title: pH dependence of the enzymatic processing of collagen I by MMP-1 (fibroblast collagenase), MMP-2 (gelatinase A), and MMP-14 ectodomain.
abstract: The proteolytic processing of collagen I by three matrix metalloproteinases (MMPs), a collagenase (MMP-1), a gelatinase (MMP-2), and the ectodomain of a membrane-type metalloproteinase (MMP-14), has been investigated at 37 °C between pH 6.0 and 9.2, a pH range reflecting conditions found in different body compartments under various physiopathological processes. In the proteolytic degradation the native collagen triple helix must be partially unwound to allow the binding of α chains to the protease's active-site cleft. We have found that MMP-1 interacts with the two types of collagen I α chains in a similar fashion, whereas both MMP-2 and MMP-14 bind the two α chains in a different way. The overall enzymatic activity is higher on the α-2 chain for both MMP-1 and MMP-2, whereas the MMP-14 ectodomain preferentially cleaves the α-1 chain. In MMP-2 a marked difference for substrate affinity (higher for the α-1 chain) is overwhelmed by an even more marked propensity to cleave the α-2 chain. As a whole, the three classes of MMPs investigated appear to process collagen I in a significantly different fashion, so various MMPs play different roles in the collagen homeostasis in various compartments (such as bloodstream, synovial fluid, normal and tumoral tissues), where different pH values are observed.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Roma Tor Vergata, Via Montpellier 1, 00133, Rome, Italy.
authors.forename: Magda
authors.initials: M
authors.lastname: Gioia
authors.forename: Giovanni Francesco
authors.initials: GF
authors.lastname: Fasciglione
authors.forename: Susanna
authors.initials: S
authors.lastname: Monaco
authors.forename: Riccardo
authors.initials: R
authors.lastname: Iundusi
authors.forename: Diego
authors.initials: D
authors.lastname: Sbardella
authors.forename: Stefano
authors.initials: S
authors.lastname: Marini
authors.forename: Umberto
authors.initials: U
authors.lastname: Tarantino
authors.forename: Massimo
authors.initials: M
authors.lastname: Coletta
mesh_terms: D024042:Collagen Type I / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D020781:Matrix Metalloproteinase 1 / Q000737:chemistry / Q000378:metabolism*; D053508:Matrix Metalloproteinase 12 / Q000737:chemistry / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry / Q000378:metabolism*; D011347:Procollagen / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D024042:Collagen Type I; D011347:Procollagen; D011994:Recombinant Proteins; D020778:Matrix Metalloproteinase 2; D053508:Matrix Metalloproteinase 12; D020781:Matrix Metalloproteinase 1