Assembly of collagen fibrils and other multimeric structures (Homo sapiens)

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25, 342014, 1810, 159, 1911, 23, 24383, 301, 36332117, 3994, 16, 375, 12, 26211427318, 3319, 28629, 32772229, 32cytosol3x4Hyp-COL6A1 3x4Hyp-GalHyl-COL6A1 Collagen type Ifibril with freehydroxylysinesLAMB3 4-hydroxyprolyl collagen alpha-1(XI) chain Collagen type VII-NC2 hexamerCTSS Collagen type II fibril Collagen type III fibre 5-hydroxylysyl-collagen alpha-1(XI) chain 3x4Hyp-GalHyl-COL9A3 GalHyl-COL2A1(182-1241) 3x4Hyp-3Hyp-COL8A2 COL15A1(1212-1388)3x4Hyp-3Hyp-5Hyl-COL1A2 MMP20 Collagen type II fibril 5Hyl-COL15A1(28-1388) Collagen type XII fibril Collagen type XII,XIV fibrils3x4Hyp-3Hyp-GlcGalHyl-COL2A1(182-1241) 5Hyl-COL8A2 3x4Hyp-3Hyp-5Hyl-COL9A2 COL3A1 Collagen type IV alpha3.alpha4.alpha5 network 3x4Hyp-GalHyl-COL2A1(182-1241) 3x4Hyp-3Hyp-GlcGalHyl-COL10A1 3,4-Hyp 5-Hyl-collagen alpha-1(XI) chain COL18A1(1572-11754)3x4Hyp-3Hyp-GalHyl-COL8A1(28-744) 3x4Hyp-GalHyl-COL7A1 3x4Hyp-GalHyl-COL1A2 3,4-hydroxyprolyl-collagen alpha-1(XI) chain 3x4Hyp-GlcGalHyl-COL9A2 3x4Hyp-GlcGalHyl-COL1A2 DST-3 GalHyl-COL9A1 5Hyl-COL9A2 3x4Hyp-5Hyl-COL1A1 3x4Hyp-3Hyp-GalHyl-COL18A1(24-1754) COL10A1 3x4Hyp-5Hyl-COL7A1(17-2821) LAMC2 3x4Hyp-GalHyl-COL10A1 3x4Hyp-COL10A1 GalHyl-COL9A2 3x4Hyp-3Hyp-GlcGalHyl-COL7A1 3x4Hyp-3Hyp-5Hyl-COL18A1(24-1754) Sulfilimine-containing collagen type IV alpha3.alpha4.alpha5 network Type I hemidesmosomecomplex3x4Hyp-3Hyp-COL1A1 3x4Hyp-3Hyp-GalHyl-COL8A2 5Hyl-COL9A3 3x4Hyp-GlcGalHyl-COL6A2 TLL1 4-Hyp 5-Hyl collagen alpha-2(XI) chain 3x4Hyp-3Hyp-GlcGalHyl-COL9A1 Br- GalHyl-COL7A1 GlcGalHyl-COL6A2 3x4Hyp-5Hyl-COL9A1 3x4Hyp-GalHyl-COL9A1 PXDN:Br-3x4Hyp-3Hyp-5Hyl-COL7A1 Collagen type I fibril Collagen type XXIV fibre COL1A1 COL27A1 3,4-Hyp 5-Gal-Hyl-collagen alpha-1(XI) chain LOXL4(25-?) 3x4Hyp-GalHyl-COL27A1 LAMC2 BPAG1e:PlectinLOXL2(26-?) Collagen type XIV Collagen type XI fibril 3x4Hyp-3Hyp-GalHyl-COL9A3 MMP7(95-267) Collagen IVCollagen type XIfibrilCOL24A1(?-?) 3x4Hyp-COL3A1 3x4Hyp-COL1A2 3x4Hyp-3Hyp-GlcGalHyl-COL9A2 GlcGalHyl-COL2A1(182-1241) 3x4Hyp-3Hyp-5Hyl-COL6A1 GlcGalHyl-COL9A2 3x4Hyp-3Hyp-GalHyl-COL15A1(28-1388) Collagen alpha-6(VI) chains 3x4Hyp-5Hyl-COL9A2 3x4Hyp-GlcGalHyl-COL9A3 5Hyl-COL2A1(182-1241) 3x4Hyp-3Hyp-GlcGalHyl-COL9A3 3x4Hyp-3Hyp-5Hyl-COL8A1(28-744) 3Hyp-4Hyp-COL9A3 3x4Hyp-GalHyl-COL3A1 GlcGalHyl-COL9A3 LOXL3(?-753) 3x4Hyp-COL9A3 GlcGalHyl-COL7A1 GlcGalHyl-COL7A1(17-2821) Glu-Gal-Hyl-collagen alpha-1(XI) chain 3x4Hyp-3Hyp-GlcGalHyl-COL15A1(28-1388) 5Hyl-COL7A1(2822-2944) TLL2 Collagentype1fibrilscross-linkedbydehydro-lysinonorleucine crosslinks5Hyl-COL7A1 Prolysyl oxidasesCollagen type I fibril with deH-HLNL 3x4Hyp-3Hyp-GalHyl-COL24A1(?-?) 3x4Hyp-5Hyl-COL9A2 3x4Hyp-5Hyl-COL9A3 3x4Hyp-3Hyp-5Hyl-COL9A2 3x4Hyp-3Hyp-GlcGalHyl-COL7A1 Collagen type I fibril GlcGalHyl-COL8A1(28-744) 3x4Hyp-3Hyp-COL9A1 Collagen type IV alpha3.alpha4.alpha5 network 3x4Hyp-COL7A1 Collagen type XV3x4Hyp-GalHyl-COL9A3 3x4Hyp-3Hyp-COL7A1(17-2821) 3x4Hyp-5Hyl-COL9A1 Collagen type X:typeII fibrils5Hyl-COL1A1 GlcGalHyl-COL15A1(28-1388) 3x4Hyp-COL9A3 LAMA3 Collagen type XVIIfibril:Integrinalpha6beta43x4Hyp-3Hyp-GlcGalHyl-COL6A2 COL9A2 3x4Hyp-GalHyl-COL8A1(28-744) 3x4Hyp-5Hyl-COL15A1(28-1388) Collagen typeI,II:XII,XIVfibrilsGlcGalHyl-COL3A1(154-1241) Collagen type I fibril LOXL2(?-774) Collagen type I fibril with lysyl-pyridinoline cross-links 3x4Hyp-COL8A1(?-744) Collagen type II fibril Collagen type IV alpha1.alpha1.alpha2 network 3x4Hyp-3Hyp-GalHyl-COL1A1 3x4Hyp-3Hyp-GlcGalHyl-COL7A1(17-2821) COL8A1(28-744) 3x4Hyp-5Hyl-COL2A1(182-1241) 3x4Hyp-GalHyl-COL1A1 3x4Hyp-GlcGalHyl-COL9A2 3x4Hyp-GlcGalHyl-COL9A1 3x4Hyp-3Hyp-GalHyl-COL7A1 3x4Hyp-3Hyp-COL9A2 3x4Hyp-COL9A2 Collagen type Ifibril withhydroxyallysines3x4Hyp-5Hyl-COL3A1 4-Hyp Glu-Gal-Hyl-collagen alpha-1(XI) chain 5Hyl-COL27A1 Collagen type I fibril 3x4Hyp-GlcGalHyl-COL6A1 3x4Hyp-3Hyp-GlcGalHyl-COL9A2 LOXL2(?-774) 3x4Hyp-GlcGalHyl-COL15A1(28-1388) Collagen type IV alpha1.alpha1.alpha2 network ITGB4 O2Collagen type VI network Collagen type I fibril Collagen networksCOL9A2 3x4Hyp-GalHyl-COL7A1(17-2821) ITGB4 3,4-hydroxyprolyl collagen alpha-2(XI) chain Collagen type I fibril 3x4Hyp-3Hyp-GalHyl-COL9A1 3x4Hyp-GalHyl-COL15A1(28-1388) BMP1 Laminin-3323x4Hyp-GlcGalHyl-COL7A1 3x4Hyp-5Hyl-COL18A1(24-1754) 3x4Hyp-COL9A1 CTSL(292-333) Collagen type IV alpha1.alpha2.alpha5.alpha6 network 3x4Hyp-GlcGalHyl-COL8A1(28-744) 3x4Hyp-GalHyl-COL9A2 GlcGalHyl-COL9A1 GlcGalHyl-COL6A1 3x4Hyp-3Hyp-5Hyl-COL7A1(2822-2944) 3x4Hyp-GalHyl-COL9A1 3,4-Hyp 5-Gal-Hyl-collagen alpha-2(XI) chain CTSL2 3x4Hyp-GalHyl-COL8A2 3x4Hyp-3Hyp-COL6A2 3x4Hyp-GlcGalHyl-COL7A1 COL1A2 Collagen type VII fibril MMP3(100-477) Collagen type XIV COL8A2 CD151Collagen alpha-5(VI) chains Collagen type I fibril GalHyl-COL9A2 3x4Hyp-3Hyp-GlcGalHyl-COL6A1 ITGA6(24-1130) COL18A1(?-1571)PCOLCE Collagen type I fibril with lysino-5-ketonorleucine cross-links LOX(22-168) Collagen alpha-2(XI) chain 3x4Hyp-3Hyp-GlcGalHyl-COL1A1 3x4Hyp-GlcGalHyl-COL7A1(17-2821) LAMB3 LOXL4 Collagen type I fibril with hydroxylysyl-pyridinoline cross-links 3x4Hyp-3Hyp-COL9A1 3x4Hyp-3Hyp-GlcGalHyl-COL27A1 ITGA6(24-1130) LAMA3 3x4Hyp-GalHyl-COL9A2 Collagen type VIII network 3x4Hyp-3Hyp-5Hyl-COL7A1(17-2821) 3x4Hyp-GlcGalHyl-COL18A1(24-1754) GalHyl-COL8A2 Collagen alpha-3(VI) chains 3x4Hyp-3Hyp-5Hyl-COL3A1 COL7A1(17-2821) Collagen type I fibril with lysyl-pyrrole cross-links 5Hyl-COL18A1(24-1754) Collagen type I fibril with hydroxylysino-5-ketonorleucine crosslinks 3x4Hyp-3Hyp-GalHyl-COL6A1 PLEC BMP1 3x4Hyp-3Hyp-GlcGalHyl-COL18A1(24-1754) 3x4Hyp-GalHyl-COL18A1(24-1754) Collagen type Ifibrils withlysyl-pyrrolecross-links3x4Hyp-3Hyp-GlcGalHyl-COL8A2 Collagen type XnetworkGlcGalHyl-COL27A1 Collagen type II fibril Collagen type XXVII fibre PLEC COL9A3 3Hyp-4Hyp-COL9A3 3x4Hyp-3Hyp-GalHyl-COL9A2 Collagen type I fibril Sulfilimine-containing collagen type IV alpha1.alpha2.alpha5.alpha6 network GlcGalHyl-COL1A2 3x4Hyp-3Hyp-5Hyl-COL24A1(?-?) Collagen type I fibril with deH-HLNL Collagen type VII fibril LOXL2 3x4Hyp-3Hyp-COL7A1 GlcGalHyl-COL7A1(2822-2944) NH33x4Hyp-3Hyp-5Hyl-COL1A1 3x4Hyp-COL8A2 3,4-Hyp Glu-Gal-Hyl-collagen alpha-2(XI) chain 3x4Hyp-3Hyp-COL18A1(24-1754) 3x4Hyp-COL7A1(2822-2944) LOXL1 Collagen type X network LOXL3 GlcGalHyl-COL9A3 Collagenalpha-1(VII) NC2region3x4Hyp-GlcGalHyl-COL9A1 COL9A1 3x4Hyp-3Hyp-5Hyl-COL9A1 3x4Hyp-3Hyp-5Hyl-COL9A3 GalHyl-COL18A1(24-1754) Collagen type VIINC2 proteinases3x4Hyp-5Hyl-COL10A1 TLL2 Collagen type II fibre 3x4Hyp-3Hyp-GlcGalHyl-COL3A1 Collagen type VIIfibril:Laminin-332Collagen type VIIhexamer3x4Hyp-COL2A1(182-1241) 5Hyl-COL10A1 GalHyl-COL3A1 GlcGalHyl-COL7A1 3x4Hyp-GalHyl-COL24A1(?-?) 4-Hyp 5-Gal-Hyl-collagen alpha-1(XI) chain GalHyl-COL9A3 3x4Hyp-3Hyp-GlcGalHyl-COL9A1 Collagen type XXIV fibril Collagen type V fibre Collagen type I fibril 5Hyl-COL6A1 LOXL1(26-94) 5Hyl-COL9A1 3x4Hyp-3Hyp-COL9A2 CollagentypeIfibrilswithhydroxylysyl-pyridinoline cross-linksCollagen type XVIIICollagen type Ifibrils withdeH-HLNLcross-links3x4Hyp-5Hyl-COL27A1 H2O2Collagen type I fibre 3x4Hyp-5Hyl-COL7A1 COL7A1 LAMA3 3x4Hyp-3Hyp-COL7A1(2822-2944) MMP13 Endostatin releasingproteases3x4Hyp-GlcGalHyl-COL8A2 3x4Hyp-3Hyp-5Hyl-COL8A2 GalHyl-COL9A3 GalHyl-COL15A1(28-1388) 3x4Hyp-3Hyp-GalHyl-COL2A1(182-1241) GalHyl-COL1A2 GalHyl-COL9A1 Collagen type Ifibril5-hydroxylysyl-collagen alpha-2(XI) chain PXDN LOX 3x4Hyp-GalHyl-COL6A2 LOXL3(26-?) 3x4Hyp-3Hyp-5Hyl-COL27A1 Collagen type I fibril 3x4Hyp-3Hyp-5Hyl-COL10A1 Glu-Gal-Hyl collagen alpha-2(XI) chain 3x4Hyp-5Hyl-COL24A1(?-?) 3x4Hyp-COL18A1(24-1754) 3x4Hyp-5Hyl-COL7A1 4-Hyp 5-Gal-Hyl collagen alpha-2(XI) chain LAMC2 COL15A1(28-1388) GalHyl-COL10A1 3x4Hyp-GalHyl-COL7A1 3x4Hyp-3Hyp-GalHyl-COL7A1(2822-2944) Tropocollagen type IV 3x4Hyp-3Hyp-GalHyl-COL7A1 COL6A1 5Hyl-COL9A3 LOXL4(?-756) ProcollagenC-proteinasesCollagen type I fibril GlcGalHyl-COL1A1 Collagen type VIIfibrilGlcGalHyl-COL9A2 3x4Hyp-GlcGalHyl-COL27A1 3x4Hyp-3Hyp-GalHyl-COL10A1 COL7A1 Collagen type XXVII fibril GlcGalHyl-COL10A1 LAMC2 Collagen type X network 3x4Hyp-GlcGalHyl-COL9A3 DST-3 MMP9(107-707) Collagen type I fibril with hydroxylysyl-pyrrole cross-links LOX(22-417) 3x4Hyp-3Hyp-5Hyl-COL9A3 LOXL4(?-756) GalHyl-COL27A1 3x4Hyp-GlcGalHyl-COL2A1(182-1241) Anchoring fibrilcomplex5Hyl-COL8A1(28-744) 5Hyl-COL3A1 GalHyl-COL7A1(2822-2944) Lysyl oxidasepropeptidesGalHyl-COL24A1(?-?) 3x4Hyp-5Hyl-COL6A2 5Hyl-COL9A1 Collagen type Ifibrils withlysyl-pyridinolinecross-linksCollagen V 3x4Hyp-COL9A1 5-Gal-Hyl-collagen alpha-1(XI) chain 3x4Hyp-COL1A1 5Hyl-COL24A1(?-?) GalHyl-COL6A2 CTSB(80-126) 3x4Hyp-COL24A1(?-?) 3x4Hyp-3Hyp-GlcGalHyl-COL7A1(2822-2944) 3x4Hyp-3Hyp-GalHyl-COL9A1 3x4Hyp-3Hyp-GalHyl-COL3A1 3x4Hyp-3Hyp-GlcGalHyl-COL8A1(28-744) COL9A1 COL7A1(2822-2944) GalHyl-COL1A1 TropocollagensLOXL1(26-574) 3x4Hyp-3Hyp-COL7A1 Network formingtropocollagensLAMA3 Collagen type XI fibril 5-Gal-Hyl collagen alpha-2(XI) chain Collagen type Ifibril withallysines3x4Hyp-COL6A2 3x4Hyp-3Hyp-GalHyl-COL9A3 Collagen type I fibril 5Hyl-COL1A2 3x4Hyp-3Hyp-5Hyl-COL2A1(182-1241) LAMB3 Lysyl oxidasesLOXL3(?-753) 3x4Hyp-3Hyp-COL1A2 GlcGalHyl-COL9A1 3x4Hyp-3Hyp-COL15A1(28-1388) GalHyl-COL7A1(17-2821) 3x4Hyp-3Hyp-COL6A1 Collagen alpha-1(XI) chain H2O2GlcGalHyl-COL8A2 Sulfilimine-containing collagen type IV alpha1.alpha1.alpha2 network H2OCOL2A1(182-1241) COL18A1(24-1754) 3x4Hyp-5Hyl-COL6A1 Collagen fibresCollagen type I, IIfibrils3x4Hyp-COL7A1 3x4Hyp-3Hyp-GlcGalHyl-COL24A1(?-?) 4-hydroxyprolyl collagen alpha-2(XI) chain GalHyl-COL6A1 LOX Collagen type IV alpha1.alpha2.alpha5.alpha6 network Collagen type XI fibre CD151 Collagen IV Collagen type II fibril 5Hyl-COL9A2 GalHyl-COL7A1 Collagen type VII fibril Tropocollagen type V 3x4Hyp-3Hyp-5Hyl-COL7A1 4-Hyp Glu-Gal-Hyl collagen alpha-2(XI) chain 3x4Hyp-3Hyp-5Hyl-COL9A1 LAMB3 3x4Hyp-GlcGalHyl-COL3A1 Collagen type XIfibril:Collagentype II fibril3x4Hyp-3Hyp-GlcGalHyl-COL1A2 5Hyl-COL7A1(17-2821) 3x4Hyp-3Hyp-5Hyl-COL15A1(28-1388) Collagen type XII fibril 3x4Hyp-GlcGalHyl-COL24A1(?-?) 3x4Hyp-3Hyp-GalHyl-COL27A1 3x4Hyp-3Hyp-5Hyl-COL6A2 CollagentypeIfibrilswithhistidino-hydroxylysinoleucine cross-links3x4Hyp-3Hyp-COL8A1(28-744) COL9A3 GalHyl-COL8A1(28-744) 3x4Hyp-3Hyp-COL3A1 COL6A2 CTSL(114-288) 3x4Hyp-3Hyp-GalHyl-COL6A2 3,4-Hyp Glu-Gal-Hyl-collagen alpha-1(XI) chain Collagen type XVII fibril 3x4Hyp-COL9A2 Cu2+ 3x4Hyp-3Hyp-COL10A1 GlcGalHyl-COL18A1(24-1754) 3x4Hyp-5Hyl-COL8A2 3x4Hyp-3Hyp-GalHyl-COL7A1(17-2821) 4-Hyp 5-Hyl-collagen alpha-1(XI) chain Collagenalpha-1(VII) trimerCollagen type II fibril 3x4Hyp-3Hyp-COL27A1 Collagen type IIfibril:Collagentype IXCollagentypeIfibrilswithhydroxylysino-5-ketonorleucine crosslinksCollagen type I fibril with dehydro-lysinonorleucine Collagen type IVnetworks withsulfiliminecross-links3x4Hyp-COL7A1(17-2821) 3x4Hyp-3Hyp-GalHyl-COL9A2 CollagentypeIfibrilswithlysino-5-ketonorleucine cross-linksCollagen type XVII fibril 3,4-Hyp 5-Hyl-collagen alpha-2(XI) chain 3x4Hyp-5Hyl-COL7A1(2822-2944) 3x4Hyp-GlcGalHyl-COL10A1 Collagen type IIfibrilGlcGalHyl-COL24A1(?-?) H2OCollagen type IX3x4Hyp-5Hyl-COL8A1(28-744) 3x4Hyp-3Hyp-COL24A1(?-?) Collagen type III fibril CollagentypeIfibrilswithhydroxylysyl-pyrrole cross-links3x4Hyp-COL15A1(28-1388) 3x4Hyp-3Hyp-GlcGalHyl-COL9A3 3x4Hyp-COL27A1 Collagen type I fibril 3x4Hyp-GalHyl-COL7A1(2822-2944) 3x4Hyp-3Hyp-GalHyl-COL1A2 Collagen fibrilsLOXL1 3x4Hyp-5Hyl-COL9A3 5Hyl-COL6A2 3x4Hyp-5Hyl-COL1A2 TLL1 3x4Hyp-GlcGalHyl-COL7A1(2822-2944) 3x4Hyp-GlcGalHyl-COL1A1 Lysyl oxidases:Cu2+3x4Hyp-3Hyp-COL2A1(182-1241) COL15A1(?-1211)5Hyl-COL7A1 2, 3513


Collagen trimers in triple-helical form, referred to as procollagen or collagen molecules, are exported from the ER and trafficked through the Golgi network before secretion into the extracellular space. For fibrillar collagens namely types I, II, III, V, XI, XXIV and XXVII (Gordon & Hahn 2010, Ricard-Blum 2011) secretion is concomitant with processing of the N and C terminal collagen propeptides. These processed molecules are known as tropocollagens, considered to be the units of higher order collagen structures. They form within the extracellular space via a process that can proceed spontaneously, but in the cellular environment is regulated by many collagen binding proteins such as the FACIT (Fibril Associated Collagens with Interrupted Triple helices) family collagens and Small Leucine-Rich Proteoglycans (SLRPs). The architecture formed ultimately depends on the collagen subtype and the cellular conditions. Structures include the well-known fibrils and fibres formed by the major structural collagens type I and II plus several different types of supramolecular assembly (Bruckner 2010). The mechanical and physical properties of tissues depend on the spatial arrangement and composition of these collagen-containing structures (Kadler et al. 1996, Shoulders & Raines 2009, Birk & Bruckner 2011).

Fibrillar collagen structures are frequently heterotypic, composed of a major collagen type in association with smaller amounts of other types, e.g. type I collagen fibrils are associated with types III and V, while type II fibrils frequently contain types IX and XI (Wess 2005). Fibres composed exclusively of a single collagen type probably do not exist, as type I and II fibrils require collagens V and XI respectively as nucleators (Kadler et al. 2008, Wenstrup et al. 2011). Much of the structural understanding of collagen fibrils has been obtained with fibril-forming collagens, particularly type I, but some central features are believed to apply to at least the other fibrillar collagen subtypes (Wess 2005). Fibril diameter and length varies considerably, depending on the tissue and collagen types (Fang et al. 2012). The reasons for this are poorly understood (Wess 2005).

Some tissues such as skin have fibres that are approximately the same diameter while others such as tendon or cartilage have a bimodal distribution of thick and thin fibrils. Mature type I collagen fibrils in tendon are up to 1 cm in length, with a diameter of approx. 500 nm. An individual fibrillar collagen triple helix is less than 1.5 nm in diameter and around 300 nm long; collagen molecules must assemble to give rise to the higher-order fibril structure, a process known as fibrillogenesis, prevented by the presence of C-terminal propeptides (Kadler et al. 1987). In electron micrographs, fibrils have a banded appearance, due to regular gaps where fewer collagen molecules overlap, which occur because the fibrils are aligned in a quarter-stagger arrangement (Hodge & Petruska 1963). Collagen microfibrils are believed to have a quasi-hexagonal unit cell, with tropocollagen arranged to form supertwisted, right-handed microfibrils that interdigitate with neighbouring microfibrils, leading to a spiral-like structure for the mature collagen fibril (Orgel et al. 2006, Holmes & Kadler 2006).

Neighbouring tropocollagen monomers interact with each other and are cross-linked covalently by lysyl oxidase (Orgel et al. 2000, Maki 2006). Mature collagen fibrils are stabilized by lysyl oxidase-mediated cross-links. Hydroxylysyl pyridinoline and lysyl pyridinoline cross-links form between (hydroxy) lysine and hydroxylysine residues in bone and cartilage (Eyre et al. 1984). Arginoline cross-links can form in cartilage (Eyre et al. 2010); mature bovine articular cartilage contains roughly equimolar amounts of arginoline and hydroxylysyl pyridinoline based on peptide yields. Mature collagen fibrils in skin are stabilized by the lysyl oxidase-mediated cross-link histidinohydroxylysinonorleucine (Yamauch et al. 1987). Due to the quarter-staggered arrangement of collagen molecules in a fibril, telopeptides most often interact with the triple helix of a neighbouring collagen molecule in the fibril, except for collagen molecules in register staggered by 4D from another collagen molecule. Fibril aggregation in vitro can be unipolar or bipolar, influenced by temperature and levels of C-proteinase, suggesting a role for the N- and C- propeptides in regulation of the aggregation process (Kadler et al. 1996). In vivo, collagen molecules at the fibril surface may retain their N-propeptides, suggesting that this may limit further accretion, or alternatively represents a transient stage in a model whereby fibrils grow in diameter through a cycle of deposition, cleavage and further deposition (Chapman 1989).

In vivo, fibrils are often composed from more than one type of collagen. Type III collagen is found associated with type I collagen in dermal fibrils, with the collagen III on the periphery, suggesting a regulatory role (Fleischmajer et al. 1990). Type V collagen associates with type I collagen fibrils, where it may limit fibril diameter (Birk et al. 1990, White et al. 1997). Type IX associates with the surface of narrow diameter collagen II fibrils in cartilage and the cornea (Wu et al. 1992, Eyre et al. 2004). Highly specific patterns of crosslinking sites suggest that collagen IX functions in interfibrillar networking (Wess 2005). Type XII and XIV collagens are localized near the surface of banded collagen I fibrils (Nishiyama et al. 1994). Certain fibril-associated collagens with interrupted triple helices (FACITs) associate with the surface of collagen fibrils, where they may serve to limit fibril fusion and thereby regulate fibril diameter (Gordon & Hahn 2010). Collagen XV, a member of the multiplexin family, is almost exclusively associated with the fibrillar collagen network, in very close proximity to the basement membrane. In human tissues collagen XV is seen linking banded collagen fibers subjacent to the basement membrane (Amenta et al. 2005). Type XIV collagen, SLRPs and discoidin domain receptors also regulate fibrillogenesis (Ansorge et al. 2009, Kalamajski et al. 2010, Flynn et al. 2010).

Collagen IX is cross-linked to the surface of collagen type II fibrils (Eyre et al. 1987). Type XII and XIV collagens are found in association with type I (Walchli et al. 1994) and type II (Watt et al. 1992, Eyre 2002) fibrils in cartilage. They are thought to associate non-covalently via their COL1/NC1 domains (Watt et al. 1992, Eyre 2002).

Some non-fibrillar collagens form supramolecular assemblies that are distinct from typical fibrils. Collagen VII forms anchoring fibrils, composed of antiparallel dimers that connect the dermis to the epidermis (Bruckner-Tuderman 2009). During fibrillogenesis, the nascent type VII procollagen molecules dimerize in an antiparallel manner. The C-propeptides are then removed by Bone morphogenetic protein 1 (Rattenholl et al. 2002) and the processed antiparallel dimers aggregate laterally. Collagens VIII and X form hexagonal networks and collagen VI forms beaded filament (Gordon & Hahn 2010, Ricard-Blum et al. 2011). View original pathway at Reactome.


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118517view09:58, 28 May 2021EweitzOntology Term : 'peptide and protein metabolic pathway' added !
114642view16:10, 25 January 2021ReactomeTeamReactome version 75
113090view11:15, 2 November 2020ReactomeTeamReactome version 74
112324view15:24, 9 October 2020ReactomeTeamReactome version 73
101223view11:11, 1 November 2018ReactomeTeamreactome version 66
100761view20:37, 31 October 2018ReactomeTeamreactome version 65
100305view19:14, 31 October 2018ReactomeTeamreactome version 64
99852view15:58, 31 October 2018ReactomeTeamreactome version 63
99409view14:34, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93410view11:22, 9 August 2017ReactomeTeamreactome version 61
86500view09:19, 11 July 2016ReactomeTeamreactome version 56
83231view10:26, 18 November 2015ReactomeTeamVersion54
81628view13:10, 21 August 2015ReactomeTeamVersion53
77089view08:38, 17 July 2014ReactomeTeamFixed remaining interactions
76795view12:17, 16 July 2014ReactomeTeamFixed remaining interactions
76118view10:18, 11 June 2014ReactomeTeamRe-fixing comment source
75830view11:39, 10 June 2014ReactomeTeamReactome 48 Update
75191view09:40, 9 May 2014Anwesha
74835view10:06, 30 April 2014ReactomeTeamNew pathway

External references


View all...
NameTypeDatabase referenceComment
3,4-Hyp 5-Gal-Hyl-collagen alpha-1(XI) chain ProteinP12107 (Uniprot-TrEMBL)
3,4-Hyp 5-Gal-Hyl-collagen alpha-2(XI) chain ProteinP13942 (Uniprot-TrEMBL)
3,4-Hyp 5-Hyl-collagen alpha-1(XI) chain ProteinP12107 (Uniprot-TrEMBL)
3,4-Hyp 5-Hyl-collagen alpha-2(XI) chain ProteinP13942 (Uniprot-TrEMBL)
3,4-Hyp Glu-Gal-Hyl-collagen alpha-1(XI) chain ProteinP12107 (Uniprot-TrEMBL)
3,4-Hyp Glu-Gal-Hyl-collagen alpha-2(XI) chain ProteinP13942 (Uniprot-TrEMBL)
3,4-hydroxyprolyl collagen alpha-2(XI) chain ProteinP13942 (Uniprot-TrEMBL)
3,4-hydroxyprolyl-collagen alpha-1(XI) chain ProteinP12107 (Uniprot-TrEMBL)
3Hyp-4Hyp-COL9A3 ProteinQ14050 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL10A1 ProteinQ03692 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL15A1(28-1388) ProteinP39059 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL18A1(24-1754) ProteinP39060 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL1A1 ProteinP02452 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL1A2 ProteinP08123 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL24A1(?-?) ProteinQ17RW2 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL27A1 ProteinQ8IZC6 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL2A1(182-1241) ProteinP02458 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL3A1 ProteinP02461 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL6A1 ProteinP12109 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL6A2 ProteinP12110 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL7A1 ProteinQ02388 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL7A1(17-2821) ProteinQ02388 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL7A1(2822-2944) ProteinQ02388 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL8A1(28-744) ProteinP27658 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL8A2 ProteinP25067 (Uniprot-TrEMBL)