View source for Collagen/ja

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[[Image:Collagentriplehelix.png|thumb|upright=1.5|トロポコラーゲン分子：3つの左巻きプロコラーゲン（赤、緑、青）が結合し、右巻き三重らせんトロポコラーゲンを形成する。]]

'''コラーゲン'''({{IPAc-en|ˈ|k|ɒ|l|ə|dʒ|ə|n}})は、主に[[cartilage/ja|軟骨]]、[[bone/ja|骨]]、[[tendon/ja|腱]]、[[ligament/ja|靭帯]]、[[skin/ja|皮膚]]などの身体の様々な[[connective tissue/ja|結合組織]]に見られる[[extracellular matrix/ja|細胞外マトリックス]]の主要な構造[[protein/ja|タンパク質]]である。結合組織の主成分として、哺乳類において最も豊富なタンパク質であり、全身のタンパク質含有量の25%から35%を占める。コラーゲンは[[amino acid/ja|アミノ酸]]が結合して[[collagen helix/ja|コラーゲンヘリックス]]として知られる細長い[[fibril/ja|線維]]の[[triple helix/ja|三重らせん]]を形成している。[[vitamin C/ja|ビタミンC]]はコラーゲンの合成に不可欠であり、[[vitamin E/ja|ビタミンE]]はコラーゲンの産生を改善する。
[[File:HCR-FISH visualization of collagen expression in P. waltl.jpg|thumb|''[[Pleurodeles waltl/ja|P. waltl]]''におけるHCR-[[Fluorescence in situ hybridization/ja|FISH]]の可視化。]]
コラーゲン組織は、[[biomineralization/ja|ミネラルミネラリゼーション]]の程度によって、剛直（骨）かコンプライアント（腱）、あるいは剛直からコンプライアントへの勾配（軟骨）を持つ。コラーゲンは[[cornea/ja|角膜]]、[[blood vessel/ja|血管]]、[[Gut (anatomy)/ja|腸]]、[[intervertebral disc/ja|椎間板]]、歯の[[dentin/ja|象牙質]]にも豊富に存在する。[[muscle tissue/ja|筋肉組織]]では、[[endomysium/ja|内膜]]の主要な構成成分として機能する。コラーゲンは筋肉組織の1～2％を占め、[[skeletal muscle/ja|骨格筋]]組織の重量の6％を占める。[[fibroblast/ja|線維芽細胞]]はコラーゲンを作り出す最も一般的な細胞である。食品や工業用に使用される[[Gelatin/ja|ゼラチン]]は、熱、塩基性溶液、弱酸を用いて不可逆的に[[hydrolyzed/ja|加水分解]]されたコラーゲンである。

==語源{{Anchor|Etymology}}==
[[File:Collagen -- Smart-Servier (cropped).jpg|thumb|コラーゲン]]

''コラーゲン''という名称は、"[[:en:glue|接着剤]]"を意味するギリシャ語[[wikt:κόλλα#Ancient Greek|κόλλα]]（''kólla''）と、「生成」を表す接尾辞-γέν（''-gen''）に由来する。

==ヒトのタイプ{{Anchor|Human types}}==
[[human body/ja|人体]]中のコラーゲンの90％以上は[[type I collagen/ja|I型コラーゲン]]である。しかし、2011年現在、28種類のヒト・コラーゲンが同定、記述され、形成する構造によっていくつかのグループに分けられている。全てのタイプが少なくとも1つの[[triple helix/ja|三重らせん]]を含んでいる。この種類の多さは、コラーゲンの多様な機能性を示している。
* 線維性（タイプI、II、III、V、XI）
* 非線維性
** [[FACIT collagen/ja|FACIT]]（F三重らせんが中断したイブリル会合コラーゲン）（IX型、XII型、XIV型、XIX型、XXI型
** 短鎖（VIII型、X型）
** [[Basement membrane/ja|基底膜]]（IV型）
** [[multiplexin/ja|マルチプレキシン]]（中断を伴う多重三重らせんドメイン）（XV型、XVIII型）
** MACIT（三重らせんが切断された膜結合型コラーゲン）（XIII型、XVII型）
** ミクロフィブリル形成（VI型）
** アンカー線維（VII型）

最も一般的な5つのタイプがある：
* [[Type I collagen/ja|I型]]：皮膚、[[tendon/ja|腱]]、血管系、臓器、[[bone/ja|骨]]（骨の有機部分の主成分）
* [[Type II collagen/ja||II型]]： [[cartilage/ja|軟骨]]（軟骨の主なコラーゲン成分）
* [[Collagen, type III, alpha 1|III型]]：網状（[[reticular fiber/ja|網状繊維]]の主成分）、I型と並んでよく見られる。
* [[Type IV collagen/ja|IV型]]：基底膜（[[basement membrane/ja|基底膜]]の上皮分泌層）を形成する。
* [[Type-V collagen/ja|V型]]：細胞表面、毛髪、[[placenta/ja|胎盤]]を形成する。

===心臓===
4つの[[heart valve/ja|心臓弁]]リングを含むコラーゲン質の[[cardiac skeleton/ja|心骨格]]は、組織学的に、弾力的かつ特異的に心筋に結合している。[[cardiac skeleton/ja|心骨格]]には、[[interventricular septum/ja|心室間隔]]と[[atrioventricular septum/ja|房室隔]]という[[cardiac septa/ja|心室の隔壁]]も含まれる。コラーゲンの[[Cardiac stress test/ja|心臓性能]]の測定への寄与は、要約すると心臓から放出される血圧の[[fluid mechanics/ja|流体力学]]に対抗する連続的なねじり力を表す。心臓の上室と下室を仕切るコラーゲン構造は、典型的な生理学的手段によって血液と電気インパルスの両方を排除する不透過性の膜である。コラーゲンによるサポートがあれば、[[atrial fibrillation/ja|心房細動]]が[[ventricular fibrillation/ja|心室細動]]に悪化することはない。コラーゲンは、平滑筋量とともに、さまざまな密度で層になっている。コラーゲンの質量、分布、年齢、密度はすべて、血液を前後に移動させるのに必要な[[compliance (physiology)/ja|コンプライアンス]]に寄与する。個々の心臓弁膜は、可変的な[[pressure/ja|圧力]]の下で、特殊なコラーゲンによって形状に折り畳まれる。コラーゲン内の[[calcium/ja|カルシウム]]沈着は、老化の自然な機能として徐々に起こる。コラーゲンマトリックス内の石灰化した点は、血液と筋肉の動くディスプレイの中でコントラストを示し、[[cardiac imaging/ja|心臓画像]]技術の方法によって、本質的に血液の流入（[[cardiac input/ja|心臓入力]]）と血液の流出（[[cardiac output/ja|心臓出力]]）の比率を示すことができる。心臓を支えるコラーゲンの病理は[[connective tissue disease/ja|結合組織病]]の範疇で理解されている。

===骨移植===
骨格は身体の構造を形成しているため、骨折や怪我の後でも強度を維持することが不可欠である。コラーゲンは三重らせん構造を持ち、非常に強い分子であるため、骨移植に使用される。骨格の構造的完全性を損なわないので、骨に使用するのに理想的である。コラーゲンの三重らせん構造は酵素による分解を防ぎ、細胞の接着を可能にし、細胞外マトリックスの適切な組み立てに重要である。

===組織再生===
コラーゲン・スキャフォールドは、スポンジ、薄いシート、ファイバーなど、組織再生に用いられている。コラーゲンは、孔構造、透過性、親水性、生体内での安定性など、組織再生に有利な特性を持つ。コラーゲンの足場はまた、[[osteoblasts/ja|骨芽細胞]]や[[fibroblast/ja|線維芽細胞]]などの細胞の沈着を支持し、一度挿入されると成長が正常に進むように促進する。

==再建外科的用途===
コラーゲンは、重度の[[burn (injury)/ja|熱傷]]や創傷の管理に使用される[[artificial skin/ja|人工皮膚]]代替物の構築に広く使用されている。これらのコラーゲンは、ウシ、ウマ、ブタ、あるいはヒト由来であり、[[silicone/ja|シリコーン]]、[[glycosaminoglycan/ja|グリコサミノグリカン]]、[[fibroblast/ja|線維芽細胞]]、[[growth factor/ja|成長因子]]および他の物質と組み合わせて使用されることもある。

=== 創傷治癒 ===
コラーゲンは、身体の重要な天然資源のひとつであり、[[wound healing/ja|創傷治癒]]のあらゆる段階に役立つ皮膚組織の成分である。コラーゲンが創傷床で利用可能になると、創傷の閉鎖が起こる。創傷が悪化し、時には切断などの処置が必要になることもあるが、それを避けることができる。

コラーゲンは天然物であるため、天然の創傷被覆材として使用され、人工の創傷被覆材にはない特性を持っている。細菌に対する耐性があり、これは創傷被覆材にとって極めて重要である。コラーゲンには感染と闘う自然な能力があるため、傷口を無菌状態に保つのに役立つ。コラーゲンを火傷のドレッシング材として使用すると、健康な[[granulation tissue/ja|肉芽組織]]が火傷の上に非常に早く形成され、火傷が急速に治癒するのを助ける。

創傷治癒の4つの段階を通して、コラーゲンは以下の機能を果たす：
* ガイド機能： [[collagen fibers/ja|コラーゲン線維]]は線維芽細胞を誘導する役割を果たす。線維芽細胞は結合組織マトリックスに沿って移動する。
* [[chemotactic/ja|走化性]]特性： コラーゲン線維の大きな表面積は、治癒を助ける線維形成細胞を引き寄せることができる。
* [[nucleation/ja|核形成]]： コラーゲンは、ある種の中性塩分子の存在下で、線維構造の形成を引き起こす核形成剤として働くことができる。
* [[Hemostatic/ja|止血]]作用： 血液[[platelet/ja|血小板]]はコラーゲンと相互作用して止血栓を作る。

==基礎研究==
コラーゲンは[[basic research/ja|実験室での研究]]において[[cell culture/ja|細胞培養]]に使用され、細胞の挙動や細胞と[[extracellular fluid/ja|細胞外環境]]との相互作用を研究している。コラーゲンはまた、[[3D bioprinting/ja|3Dバイオプリンティング]]や3D組織モデルの[[biofabrication/ja|バイオファブリケーション]]のための[[Bio-ink/ja|バイオインク]]としても広く使用されている。

==生物学{{Anchor|Biology}}==
コラーゲンタンパク質は三重らせんで構成され、一般に2本の同一鎖（α1）と化学組成がわずかに異なるもう1本の鎖（α2）からなる。コラーゲンのアミノ酸組成はタンパク質としては非定型であり、特に[[hydroxyproline/ja|ヒドロキシプロリン]]の含有量が高い。コラーゲンのアミノ酸配列で最も一般的なモチーフは[[glycine/ja|グリシン]]-[[proline/ja|プロリン]]-Xとグリシン-X-ヒドロキシプロリンであり、Xは[[glycine/ja|グリシン]]、[[proline/ja|プロリン]]、[[hydroxyproline/ja|ヒドロキシプロリン]]以外のアミノ酸である。魚類と哺乳類の皮膚の平均アミノ酸組成を示す。

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{| class="wikitable sortable"
|-
! Amino acid !! Abundance in mammal skin<br>([[Residue (biochemistry)|residues]]/1000) !! Abundance in fish skin<br>(residues/1000)
|-
| [[Glycine]] || 329 || 339
|-
| [[Proline]] || 126 || 108
|-
| [[Alanine]] || 109 || 114
|-
| [[Hydroxyproline]] || 95 || 67
|-
| [[Glutamic acid]] || 74 || 76
|-
| [[Arginine]] || 49 || 52
|-
| [[Aspartic acid]] || 47 || 47
|-
| [[Serine]] || 36 || 46
|-
| [[Lysine]] || 29 || 26
|-
| [[Leucine]] || 24 || 23
|-
| [[Valine]] || 22 || 21
|-
| [[Threonine]] || 19 || 26
|-
| [[Phenylalanine]] || 13 || 14
|-
| [[Isoleucine]] || 11 || 11
|-
| [[Hydroxylysine]] || 6 || 8
|-
| [[Methionine]] || 6 || 13
|-
| [[Histidine]] || 5 || 7
|-
| [[Tyrosine]] || 3 || 3
|-
| [[Cysteine]] || 1 || 1
|-
| [[Tryptophan]] || 0 || 0
|}
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==Synthesis==
First, a three-dimensional stranded structure is assembled, with the amino acids glycine and proline as its principal components. This is not yet collagen but its precursor, procollagen. Procollagen is then modified by the addition of [[hydroxyl]] groups to the amino acids [[proline]] and [[lysine]]. This step is important for later [[glycosylation]] and the formation of the triple helix structure of collagen. Because the [[hydroxylase]] enzymes that perform these reactions require [[vitamin C]] as a cofactor, a long-term deficiency in this vitamin results in impaired collagen synthesis and [[scurvy]]. and [[lysyl hydroxylase]]. The reaction consumes one ascorbate molecule per hydroxylation.
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The synthesis of collagen occurs inside and outside of the cell. The formation of collagen which results in fibrillary collagen (most common form) is discussed here. Meshwork collagen, which is often involved in the formation of filtration systems, is the other form of collagen. All types of collagens are triple helices, and the differences lie in the make-up of the alpha peptides created in step 2.
# '''Transcription of mRNA''': About 44 genes are associated with collagen formation, each coding for a specific mRNA sequence, and typically have the "''COL''" prefix. The beginning of collagen synthesis begins with turning on genes which are associated with the formation of a particular alpha peptide (typically alpha 1, 2 or 3).
# '''Pre-pro-peptide formation''': Once the final mRNA exits from the cell nucleus and enters into the cytoplasm, it links with the ribosomal subunits and the process of translation occurs. The early/first part of the new peptide is known as the signal sequence. The signal sequence on the [[N-terminal]] of the peptide is recognized by a [[signal recognition particle]] on the [[endoplasmic reticulum]], which will be responsible for directing the [[Protein precursor|pre-pro-peptide]] into the endoplasmic reticulum. Therefore, once the synthesis of new peptide is finished, it goes directly into the endoplasmic reticulum for post-translational processing. It is now known as preprocollagen.
# '''Pre-pro-peptide to pro-collagen''': Three modifications of the pre-pro-peptide occur leading to the formation of the alpha peptide:
## The signal peptide on the N-terminal is removed, and the molecule is now known as ''propeptide'' (not procollagen).
## Hydroxylation of lysines and prolines on propeptide by the enzymes 'prolyl hydroxylase' and 'lysyl hydroxylase' (to produce hydroxyproline and hydroxylysine) occurs to aid cross-linking of the alpha peptides. This enzymatic step requires [[vitamin C]] as a cofactor. In [[scurvy]], the lack of hydroxylation of prolines and lysines causes a looser triple helix (which is formed by three alpha peptides).
## Glycosylation occurs by adding either glucose or galactose monomers onto the hydroxyl groups that were placed onto lysines, but not on prolines.
## Once these modifications have taken place, three of the hydroxylated and glycosylated propeptides twist into a triple helix forming procollagen. Procollagen still has unwound ends, which will be later trimmed. At this point, the procollagen is packaged into a transfer vesicle destined for the Golgi apparatus.
# '''[[Golgi apparatus]] modification''': In the Golgi apparatus, the procollagen goes through one last post-translational modification before being secreted out of the cell. In this step, oligosaccharides (not monosaccharides as in step 3) are added, and then the procollagen is packaged into a secretory vesicle destined for the extracellular space.
# '''Formation of tropocollagen''': Once outside the cell, membrane bound enzymes known as collagen peptidases, remove the "loose ends" of the procollagen molecule. What is left is known as tropocollagen. Defects in this step produce one of the many collagenopathies known as [[Ehlers–Danlos syndrome]]. This step is absent when synthesizing type III, a type of fibrillar collagen.
# '''Formation of the collagen fibril''': [[lysyl oxidase]], an extracellular [[Copper in health|copper-dependent]] enzyme, produces the final step in the collagen synthesis pathway. This enzyme acts on lysines and hydroxylysines producing aldehyde groups, which will eventually undergo covalent bonding between tropocollagen molecules. This polymer of tropocollagen is known as a collagen fibril.
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[[File:Tropocollagen cross-linkage lysyl oxidase (EN).svg|thumb|upright=1.3|Action of [[lysyl oxidase]]]]
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===Amino acids===
Collagen has an unusual [[amino acid]] composition and sequence:
* [[Glycine]] is found at almost every third [[residue (biochemistry)|residue]].
* [[Proline]] makes up about 17% of collagen.
* Collagen contains two unusual derivative amino acids not directly inserted during [[translation (genetics)|translation]]. These amino acids are found at specific locations relative to glycine and are modified post-translationally by different enzymes, both of which require [[vitamin C]] as a [[cofactor (biochemistry)|cofactor]].
** [[Hydroxyproline]] derived from proline
** [[Hydroxylysine]] derived from [[lysine]] – depending on the type of collagen, varying numbers of hydroxylysines are [[glycosylation|glycosylated]] (mostly having [[disaccharide]]s attached).
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[[Cortisol]] stimulates [[Amide hydrolysis|degradation]] of (skin) collagen into amino acids.
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=== Collagen I formation ===
Most collagen forms in a similar manner, but the following process is typical for type I:
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# Inside the cell
## Two types of alpha chains – alpha-1 and alpha 2, are formed during [[translation (genetics)|translation]] on ribosomes along the [[rough endoplasmic reticulum]] (RER). These peptide chains known as preprocollagen, have registration peptides on each end and a [[signal peptide]].
## Polypeptide chains are released into the lumen of the RER.
## Signal peptides are cleaved inside the RER and the chains are now known as pro-alpha chains.
## [[Hydroxylation]] of [[lysine]] and [[proline]] amino acids occurs inside the lumen. This process is dependent on and consumes [[ascorbic acid]] (vitamin C) as a [[cofactor (biochemistry)|cofactor]].
## [[Glycosylation]] of specific hydroxylysine residues occurs.
## Triple alpha helical structure is formed inside the endoplasmic reticulum from two alpha-1 chains and one alpha-2 chain.
## [[Procollagen]] is shipped to the [[Golgi apparatus]], where it is packaged and secreted into extracellular space by [[exocytosis]].
# Outside the cell
## Registration peptides are cleaved and tropocollagen is formed by [[procollagen peptidase]].
## Multiple tropocollagen molecules form collagen fibrils, via covalent cross-linking ([[aldol reaction]]) by [[lysyl oxidase]] which links hydroxylysine and lysine residues. Multiple collagen fibrils form into collagen fibers.
## Collagen may be attached to cell membranes via several types of protein, including [[fibronectin]], [[laminin]], [[fibulin]] and [[integrin]].
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===Synthetic pathogenesis===
Vitamin C deficiency causes [[scurvy]], a serious and painful disease in which defective collagen prevents the formation of strong [[connective tissue]]. [[Gingiva|Gums]] deteriorate and bleed, with loss of teeth; skin discolors, and [[wound]]s do not heal. Prior to the 18th century, this condition was notorious among long-duration military, particularly naval, expeditions during which participants were deprived of foods containing vitamin C.
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An [[autoimmune disease]] such as [[lupus erythematosus]] or [[rheumatoid arthritis]] may attack healthy collagen fibers.
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Many bacteria and viruses secrete [[virulence factor]]s, such as the enzyme [[collagenase]], which destroys collagen or interferes with its production.
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==Molecular structure==
A single collagen molecule, tropocollagen, is used to make up larger collagen aggregates, such as fibrils. It is approximately 300&nbsp;[[nanometre|nm]] long and 1.5&nbsp;nm in diameter, and it is made up of three [[polypeptide]] strands (called alpha peptides, see step 2), each of which has the conformation of a left-handed [[helix]] – this should not be confused with the right-handed [[alpha helix]]. These three left-handed helices are twisted together into a right-handed triple helix or "super helix", a cooperative [[quaternary structure]] stabilized by many [[hydrogen bond]]s. With type I collagen and possibly all fibrillar collagens, if not all collagens, each triple-helix associates into a right-handed super-super-coil referred to as the collagen microfibril. Each microfibril is [[wikt:interdigitate|interdigitated]] with its neighboring microfibrils to a degree that might suggest they are individually unstable, although within collagen fibrils, they are so well ordered as to be crystalline.
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[[File:Collagen biosynthesis (en).png|thumb|upright=1.3|Three [[polypeptide]]s coil to form tropocollagen. Many tropocollagens then bind together to form a fibril, and many of these then form a fibre.]]
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A distinctive feature of collagen is the regular arrangement of [[amino acid]]s in each of the three chains of these collagen subunits. The sequence often follows the pattern [[glycine|Gly]]-[[proline|Pro]]-X or Gly-X-[[hydroxyproline|Hyp]], where X may be any of various other amino acid residues. Proline or hydroxyproline constitute about 1/6 of the total sequence. With glycine accounting for the 1/3 of the sequence, this means approximately half of the collagen sequence is not glycine, proline or hydroxyproline, a fact often missed due to the distraction of the unusual GX<sub>1</sub>X<sub>2</sub> character of collagen alpha-peptides. The high glycine content of collagen is important with respect to stabilization of the collagen helix as this allows the very close association of the collagen fibers within the molecule, facilitating hydrogen bonding and the formation of intermolecular cross-links. This kind of regular repetition and high glycine content is found in only a few other fibrous proteins, such as silk [[fibroin]].
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Collagen is not only a structural protein. Due to its key role in the determination of cell phenotype, cell adhesion, tissue regulation, and infrastructure, many sections of its non-proline-rich regions have cell or matrix association/regulation roles. The relatively high content of proline and hydroxyproline rings, with their geometrically constrained [[carboxyl]] and (secondary) [[amino]] groups, along with the rich abundance of glycine, accounts for the tendency of the individual polypeptide strands to form left-handed helices spontaneously, without any intrachain hydrogen bonding.
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Because glycine is the smallest amino acid with no side chain, it plays a unique role in fibrous structural proteins. In collagen, Gly is required at every third position because the assembly of the triple helix puts this residue at the interior (axis) of the helix, where there is no space for a larger side group than glycine's single [[hydrogen]] atom. For the same reason, the rings of the Pro and Hyp must point outward. These two amino acids help stabilize the triple helix – Hyp even more so than Pro; a lower concentration of them is required in animals such as fish, whose [[thermoregulation|body temperatures]] are lower than most warm-blooded animals. Lower proline and hydroxyproline contents are characteristic of cold-water, but not warm-water fish; the latter tend to have similar proline and hydroxyproline contents to mammals. The lower proline and hydroxyproline contents of cold-water fish and other [[poikilothermic|poikilotherm]] animals leads to their collagen having a lower thermal stability than mammalian collagen. This lower thermal stability means that [[gelatin]] derived from fish collagen is not suitable for many food and industrial applications.
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The tropocollagen [[protein subunit|subunits]] spontaneously [[molecular self-assembly|self-assemble]], with regularly staggered ends, into even larger arrays in the [[extracellular]] spaces of tissues. Additional assembly of fibrils is guided by fibroblasts, which deposit fully formed fibrils from fibripositors. In the fibrillar collagens, molecules are staggered to adjacent molecules by about 67&nbsp;[[Nanometre|nm]] (a unit that is referred to as 'D' and changes depending upon the hydration state of the aggregate). In each D-period repeat of the microfibril, there is a part containing five molecules in cross-section, called the "overlap", and a part containing only four molecules, called the "gap". These overlap and gap regions are retained as microfibrils assemble into fibrils, and are thus viewable using electron microscopy. The triple helical tropocollagens in the microfibrils are arranged in a quasihexagonal packing pattern.
[[File:Collagen fibrils in rabbit skin.jpg|thumb|upright|The D-period of collagen fibrils results in visible 67nm bands when observed by electron microscopy.]]
There is some [[covalent bond|covalent]] crosslinking within the triple helices and a variable amount of covalent crosslinking between tropocollagen helices forming well-organized aggregates (such as fibrils). Larger fibrillar bundles are formed with the aid of several different classes of proteins (including different collagen types), glycoproteins, and proteoglycans to form the different types of mature tissues from alternate combinations of the same key players. Collagen's [[soluble|insolubility]] was a barrier to the study of monomeric collagen until it was found that tropocollagen from young animals can be extracted because it is not yet fully [[cross-link|crosslinked]]. However, advances in microscopy techniques (i.e. electron microscopy (EM) and atomic force microscopy (AFM)) and X-ray diffraction have enabled researchers to obtain increasingly detailed images of collagen structure ''in situ''. These later advances are particularly important to better understanding the way in which collagen structure affects cell–cell and cell–matrix communication and how tissues are constructed in growth and repair and changed in development and disease. For example, using AFM–based nanoindentation it has been shown that a single collagen fibril is a heterogeneous material along its axial direction with significantly different mechanical properties in its gap and overlap regions, correlating with its different molecular organizations in these two regions.
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Collagen fibrils/aggregates are arranged in different combinations and concentrations in various tissues to provide varying tissue properties. In bone, entire collagen triple helices lie in a parallel, staggered array. 40&nbsp;nm gaps between the ends of the tropocollagen subunits (approximately equal to the gap region) probably serve as nucleation sites for the deposition of long, hard, fine crystals of the mineral component, which is hydroxylapatite (approximately) Ca<sub>10</sub>(OH)<sub>2</sub>(PO<sub>4</sub>)<sub>6</sub>. Type I collagen gives bone its [[tensile strength]].
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==Associated disorders==
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Collagen-related diseases most commonly arise from genetic defects or nutritional deficiencies that affect the biosynthesis, assembly, posttranslational modification, secretion, or other processes involved in normal collagen production.
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{| class="wikitable"
|-
|+'''Genetic defects of collagen genes'''
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| '''Type''' || '''Notes''' || '''Gene(s)''' || '''[[Collagen disease|Disorders]]'''
 |-
 | [[Type-I collagen|I]] || This is the most abundant collagen of the human body. It is present in [[scar]] tissue, the end product when tissue [[healing|heals]] by repair. It is found in [[tendon]]s, skin, artery walls, cornea, the [[endomysium]] surrounding muscle fibers, fibrocartilage, and the organic part of bones and teeth. || [[COL1A1]], [[COL1A2]] || [[Osteogenesis imperfecta]], [[Ehlers–Danlos syndrome]], [[infantile cortical hyperostosis]] a.k.a. Caffey's disease
 |-
 | [[Type-II collagen|II]] || [[Hyaline cartilage]], makes up 50% of all cartilage protein. [[Vitreous humour]] of the eye. || [[COL2A1]] || [[Collagenopathy, types II and XI]]
 |-
 | [[Type-III collagen|III]] || This is the collagen of [[granulation tissue]] and is produced quickly by young fibroblasts before the tougher type I collagen is synthesized. [[Reticular fiber]]. Also found in artery walls, skin, intestines and the uterus || [[COL3A1]] || [[Ehlers–Danlos syndrome]], [[Dupuytren's contracture]]
 |-
 | [[Type-IV collagen|IV]] || [[Basal lamina]]; [[eye lens]]. Also serves as part of the filtration system in [[capillaries]] and the [[Glomerulus (kidney)|glomeruli]] of [[nephron]] in the [[kidney]]. || [[Collagen, type IV, alpha 1|COL4A1]], [[COL4A2]], [[COL4A3]], [[COL4A4]], [[COL4A5]], [[COL4A6]] || [[Alport syndrome]], [[Goodpasture's syndrome]]
 |-
 | V || Most interstitial tissue, assoc. with type I, associated with [[placenta]] || [[COL5A1]], [[COL5A2]], [[COL5A3]] || [[Ehlers–Danlos syndrome]] (classical)
 |-
 | VI || Most interstitial tissue, assoc. with type I || [[COL6A1]], [[COL6A2]], [[COL6A3]], [[COL6A5]] || [[Ulrich myopathy]], [[Bethlem myopathy]], [[atopic dermatitis]]
 |-
 | VII || Forms [[anchoring fibril]]s in [[dermoepidermal junction]]s || [[COL7A1]] || [[Epidermolysis bullosa dystrophica]]
 |-
 | VIII || Some [[endothelium|endothelial]] cells || [[COL8A1]], [[COL8A2]] || [[Posterior polymorphous corneal dystrophy 2]]
 |-
 | IX || [[FACIT collagen]], cartilage, assoc. with type II and XI fibrils || [[COL9A1]], [[COL9A2]], [[COL9A3]] || [[EDM2]] and [[EDM3]]
 |-
 | X || [[Hypertrophic]] and [[Mineralization (biology)|mineralizing]] cartilage || [[COL10A1]] || [[Schmid metaphyseal dysplasia]]
 |-
 | XI || Cartilage || [[COL11A1]], [[COL11A2]] || [[Collagenopathy, types II and XI]]
 |-
 | XII || [[FACIT collagen]], interacts with type I containing fibrils, [[decorin]] and glycosaminoglycans || [[COL12A1]] || –
 |-
 | XIII || Transmembrane collagen, interacts with integrin a1b1, [[fibronectin]] and components of basement membranes like [[nidogen]] and [[perlecan]]. || [[COL13A1]] || –
 |-
 | XIV|| [[FACIT collagen]], also known as undulin || [[COL14A1]] || –
 |-
 | XV || – || [[COL15A1]] || –
 |-
 | XVI || [[FACIT collagen]] || [[COL16A1]] || –
 |-
 | [[Collagen XVII|XVII]] || Transmembrane collagen, also known as BP180, a 180 kDa protein || [[COL17A1]] || [[Bullous pemphigoid]] and certain forms of junctional [[epidermolysis bullosa]]
 |-
 | [[Type XVIII collagen|XVIII]] || Source of [[endostatin]] || [[COL18A1]] || –
 |-
 | XIX || [[FACIT collagen]] || [[COL19A1]] || –
 |-
 | XX || – || [[COL20A1]] || –
 |-
 | XXI || [[FACIT collagen]] || [[COL21A1]] || –
 |-
 | XXII || [[FACIT collagen]] || [[COL22A1]] || –
 |-
 | [[Collagen, type XXIII, alpha 1|XXIII]] || MACIT collagen || [[COL23A1]] || –
 |-
 | XXIV || – || [[COL24A1]] || –
 |-
 | XXV || – || [[COL25A1]] || –
 |-
 | XXVI || – || [[EMID2]] || –
 |-
 | XXVII || – || [[COL27A1]] || –
 |-
 | XXVIII || – || [[COL28A1]] || –
 |-
 | XXIX || Epidermal collagen || [[COL29A1]] || Atopic dermatitis
|}
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In addition to the above-mentioned disorders, excessive deposition of collagen occurs in [[scleroderma]].
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==Diseases==
One thousand mutations have been identified in 12 out of more than 20 types of collagen. These mutations can lead to various diseases at the tissue level.
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[[Osteogenesis imperfecta]] – Caused by a mutation in ''type 1 collagen'', dominant autosomal disorder, results in weak bones and irregular connective tissue, some cases can be mild while others can be lethal. Mild cases have lowered levels of collagen type 1 while severe cases have structural defects in collagen.
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[[Chondrodysplasia]]s – Skeletal disorder believed to be caused by a mutation in ''type 2 collagen'', further research is being conducted to confirm this.
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[[Ehlers–Danlos syndrome]] – Thirteen different types of this disorder, which lead to deformities in connective tissue, are known. Some of the rarer types can be lethal, leading to the rupture of arteries. Each syndrome is caused by a different mutation. For example, the vascular type (vEDS) of this disorder is caused by a mutation in ''collagen type 3''.
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[[Alport syndrome]] – Can be passed on genetically, usually as X-linked dominant, but also as both an autosomal dominant and autosomal recessive disorder, those with the condition have problems with their kidneys and eyes, loss of hearing can also develop during the childhood or adolescent years.
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[[Knobloch syndrome]] – Caused by a mutation in the [[COL18A1]] gene that codes for the production of collagen XVIII. Patients present with protrusion of the brain tissue and degeneration of the retina; an individual who has family members with the disorder is at an increased risk of developing it themselves since there is a hereditary link.
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==Characteristics==
Collagen is one of the long, [[fibrous protein|fibrous structural proteins]] whose functions are quite different from those of [[globular protein]]s, such as [[enzyme]]s. Tough bundles of collagen called ''collagen fibers'' are a major component of the [[extracellular matrix]] that supports most tissues and gives cells structure from the outside, but collagen is also found inside certain cells. Collagen has great [[tensile strength]], and is the main component of [[fascia]], [[cartilage]], [[ligament]]s, [[tendon]]s, [[bone]] and skin. Along with [[elastin]] and soft [[keratin]], it is responsible for skin strength and elasticity, and its degradation leads to [[wrinkle]]s that accompany [[aging]]. It strengthens [[blood vessel]]s and plays a role in [[biological tissue|tissue]] development. It is present in the [[cornea]] and lens of the eye in [[crystal]]line form. It may be one of the most abundant proteins in the fossil record, given that it appears to fossilize frequently, even in bones from the [[Mesozoic]] and [[Paleozoic]].
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===Uses===
[[file:Beretta Salami and Collagen Casing .jpg|right|150px|thumb|A salami and the collagen casing (below) it came in]]
Collagen has a wide variety of applications, from food to medical. In the medical industry, it is used in [[plastic surgery|cosmetic surgery]] and [[burn (injury)|burn surgery]]. In the food sector, one use example is in [[casing (sausage)|casings for sausages]].
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If collagen is subject to sufficient [[denaturation (biochemistry)|denaturation]], such as by heating, the three tropocollagen strands separate partially or completely into globular domains, containing a different secondary structure to the normal collagen polyproline II (PPII) of [[random coil]]s. This process describes the formation of [[gelatin]], which is used in many foods, including flavored [[gelatin dessert]]s. Besides food, gelatin has been used in pharmaceutical, cosmetic, and photography industries. It is also used as a [[dietary supplement]], and has been advertised as a potential remedy against the ageing process.
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From the Greek for glue, ''kolla'', the word collagen means "[[animal glue|glue]] producer" and refers to the early process of boiling the skin and [[tendon|sinews]] of horses and other animals to obtain glue. Collagen adhesive was used by Egyptians about 4,000 years ago, and Native Americans used it in [[bow (weapon)|bows]] about 1,500 years ago. The oldest glue in the world, [[radiocarbon dating|carbon-dated]] as more than 8,000 years old, was found to be collagen – used as a protective lining on rope baskets and [[embroidery|embroidered]] [[Textile|fabric]]s, to hold [[list of eating utensils|utensils]] together, and in crisscross decorations on [[human skull]]s. Collagen normally converts to gelatin, but survived due to dry conditions. Animal glues are [[thermoplastic]], softening again upon reheating, so they are still used in making [[musical instrument]]s such as fine violins and guitars, which may have to be reopened for repairs – an application incompatible with tough, [[chemical synthesis|synthetic]] plastic adhesives, which are permanent. Animal sinews and skins, including leather, have been used to make useful articles for millennia.
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Gelatin-[[resorcinol]]-[[formaldehyde]] glue (and with formaldehyde replaced by less-toxic pentanedial and [[glyoxal|ethanedial]]) has been used to repair experimental incisions in rabbit [[lung]]s.
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=== 化粧品
[[Bovine/ja|ウシ]]コラーゲンは、シワや皮膚の老化の[[:en:Aesthetics|エステティック]]矯正のための[[dermal filler/ja|皮膚充填剤]]に広く使用されている。コラーゲンの繊維は大きすぎるため皮膚に浸透しないが、コラーゲンクリームも広く販売されている。コラーゲンサプリメントに関する研究のほとんどは、肯定的な研究結果から利益を得ることができる産業によって資金提供されている。

==歴史{{Anchor|History}}==
コラーゲンの分子構造や充填構造については、何十年にもわたる研究の間、科学者たちの頭を悩ませてきた。コラーゲンが分子レベルで規則正しい構造を持っているという最初の証拠は、1930年代半ばに発表された。その後、研究はコラーゲン[[monomer/ja|モノマー]]のコンフォメーションに集中し、個々のペプチド鎖のコンフォメーションを正しく扱いながらも、いくつかの競合するモデルが生み出された。1955年に[[:en:G. N. Ramachandran|G. N. Ramachandran]]によって提唱された三重らせん状の「マドラス」モデルは、コラーゲンの[[quaternary structure/ja|四次構造]]の正確なモデルを提供した。このモデルは、20世紀後半により高い解像度の研究によって支持された。

コラーゲンの充填構造は、六角形であることは古くから知られているが、[[fibrillar/ja|線維性]]コラーゲンタイプ以外では同程度には定義されていない。コラーゲンの単量体構造と同様に、コラーゲン分子のパッキング配列は「シート状」であるか、あるいは[[microfibril/ja|ミクロフィブリル]]状であるという、いくつかの相反するモデルが提唱されている。腱、角膜、軟骨のコラーゲン線維のミクロフィブリル構造は、20世紀後半から21世紀初頭にかけて[[:en:electron microscopy|電子顕微鏡]]で直接撮影された。[[rat/ja|ラット]]尾腱のミクロフィブリル構造は、観察された構造に最も近いものとしてモデル化されたが、隣接するコラーゲン分子のトポロジカルな進行を単純化しすぎたため、''ミクロフィブリル''と呼ばれる不連続なD-周期的5量体配列の正しいコンフォメーションは予測できなかった。

==こちらも参照==
{{col div|colwidth=30em}}
* [[Collagen hybridizing peptide/ja|コラーゲンハイブリダイジングペプチド]], 変性コラーゲンに結合できるペプチド
* [[Hypermobility spectrum disorder/ja]]
* [[Metalloprotease inhibitor/ja]]
* [[Osteoid/ja|オステオイド]], 骨のコラーゲン含有成分
* [[Collagen loss/ja]]
{{colend}}

{{Commons category|Collagen}}
{{Connective tissue/ja}}

{{Fibrous proteins/ja}}

[[Category:Collagens|*]]
[[Category:Structural proteins]]
[[Category:Edible thickening agents]]
[[Category:Aging-related proteins]]