Gelatin degradation by MMP1, 2, 3, 7, 8, 9, 12, 13 Gelatin degradation by MMP19 Endostatin degradation by cathepsins Collagen type XIX degradation PathwayStep6054 PathwayStep6055 PathwayStep6056 PathwayStep6057 PathwayStep6058 PathwayStep6059 PathwayStep6050 PathwayStep6051 PathwayStep6052 PathwayStep6053 PathwayStep6067 PathwayStep6068 PathwayStep6065 PathwayStep6066 PathwayStep6069 PathwayStep6060 PathwayStep6063 PathwayStep6064 PathwayStep6061 PathwayStep6062 PathwayStep6076 PathwayStep6077 PathwayStep6078 PathwayStep6079 PathwayStep6072 PathwayStep6073 PathwayStep6074 PathwayStep6075 PathwayStep6070 PathwayStep6071 PathwayStep6080 PathwayStep6048 PathwayStep6049 Collagen type II degradation by MMP14 Collagen type VII degradation by MMP1,2,3 Collagen type III degradation by MMP10 Collagen type III degradation by MMP14 Collagen type II degradation by MMP15 Collagen type III degradation by MMP1,8,9,13 Collagen type V degradation by MMP2,9,10 Collagen type VI degradation by MMP2,9,11 Collagen type III degradation by MMP15 Collagen type IV degradation by MMP2,3,4,9,10,12 Collagen type I degradation by MMP15 Collagen type II degradation by MMP1,3,8,13,PRSS2 Collagen type I degradation by MMP1,2,8,13, PRSS2 Collagen type I degradation by MMP14 Collagen type XVII ectodomain shedding Collagen type XIII ectodomain shedding Collagen type XVIII endostatin release Collagen type XXIII ectodomain shedding Collagen type XXV ectomain shedding Collagen type VIII degradation by ELANE Collagen type VIII degradation by MMP1 Collagen type XII degradation by MMP12 Collagen type XIV degradation by MMP9,13 Collagen type XV restin release Collagen type XVI degradation by MMP9 Collagen type IX degradation by MMP3,13 Collagen type X degradation by MMP1,2 Collagen type X degradation by MMP3, 13 Collagen type XI degradation by MMP1,2,3,9 Degradation of collagen Authored: Jupe, S, 2011-07-12 Collagen fibril diameter and spatial organisation are dependent on the species, tissue type and stage of development (Parry 1988). The lengths of collagen fibrils in mature tissues are largely unknown but in tendon can be measured in millimetres (Craig et al. 1989). Collagen fibrils isolated from adult bovine corneal stroma had ~350 collagen molecules in transverse section, tapering down to three molecules at the growing tip (Holmes & Kadler 2005). <br><br>The classical view of collagenases is that they actively unwind the triple helical chain, a process termed molecular tectonics (Overall 2002, Bode & Maskos 2003), before preferentially cleaving the alpha2 chain followed by the remaining chains (Chung et al. 2004). More recently it has been suggested that collagen fibrils exist in an equilibrium between protected and vulnerable states (Stultz 2002, Nerenberg & Stultz 2008). The prototypical triple-helical structure of collagen does not fit into the active site of collagenase MMPs. In addition the scissile bonds are not solvent-exposed and are therefore inaccessible to the collagenase active site (Chung et al. 2004, Stultz 2002). It was realized that collagen must locally unfold into non-triple helical regions to allow collagenolysis. Observations using circular dichroism and differential scanning calorimetry confirm that there is considerable heterogeneity along collagen fibres (Makareeva et al. 2008) allowing access for MMPs at physiological temperatures (Salsas-Escat et al. 2010).<br><br>Collagen fibrils with cut chains are unstable and accessible to proteinases that cannot cleave intact collagen strands (Woessner & Nagase 2000, Somerville et al. 2003). Continued degradation leads to the formation of gelatin (Lovejoy et al. 1999). Degradation of collagen types other than I-III is less well characterized but believed to occur in a similar manner. <br><br>Metalloproteinases (MMPs) play a major part in the degradation of several extracellular macromolecules including collagens. MMP1 (Welgus et al. 1981), MMP8 (Hasty et al. 1987), and MMP13 (Knauper et al. 1996), sometimes referred to as collagenases I, II and III respectively, are able to initiate the intrahelical cleavage of the major fibril forming collagens I, II and III at neutral pH, and thus thought to define the rate-limiting step in normal tissue remodeling events. All can cleave additional substrates including other collagen subtypes. Collagenases cut collagen alpha chains at a single conserved Gly-Ile/Leu site approximately 3/4 of the molecule's length from the N-terminus (Fields 1991, Chung et al. 2004). The cleavage site is characterised by the motif G(I/L)(A/L); the G-I/L bond is cleaved. In collagen type I this corresponds to G953-I954 in the Uniprot canonical alpha chain sequences (often given as G775-I776 in literature). It is not clear why only this bond is cleaved, as the motif occurs at several other places in the chain. MMP14, a membrane-associated MMP also known as Membrane-type matrix metalloproteinase 1 (MT-MMP1), is able to cleave collagen types I, II and III (Ohuchi et al. 1997). Edited: Jupe, S, 2012-11-12 GENE ONTOLOGYGO:0030574 ISBN0 19 850268 0 Pubmed10074939 Pubmed11076937 Pubmed12079342 Pubmed12353914 Pubmed12801404 Pubmed12887053 Pubmed15257288 Pubmed15588825 Pubmed1666905 Pubmed18073209 Pubmed18644377 Pubmed20394413 Pubmed21087458 Pubmed2477190 Pubmed3038863 Pubmed3282560 Pubmed6270089 Pubmed8576151 Pubmed8999957 Pubmed9818170 Reactome Database ID Release 431442490 Reactome, http://www.reactome.org ReactomeREACT_150401 Reviewed: Sorsa, Timo, 2012-10-08