The collagenolytic action of MMP-1 is regulated by the interaction between the catalytic domain and the hinge region 1Giovanni Francesco Fasciglione

Magda Gioia, Hiroki Tsukada, Jian Liang, Riccardo Iundusi, Umberto Tarantino, Massimo Coletta, Tayebeh Pourmotabbed, Stefano Marini

Research output: Contribution to journalArticle

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Abstract

The role of the hinge region in the unwinding and cleavage of type I collagen by interstitial collagenase (MMP-1) has been studied at 37 C and pH 7.3. The collagenolytic processing by MMP-1 displays a very similar overall rate for both chains of collagen I, even though the affinity is higher for the a-1 chain and the cleavage rate is faster for the a-2 chain. MMP-1 binding to collagen I brings about a significant unwinding of the triple-helical arrangement only after the first cleavage step of the a-1 and a-2 chains. The proteolytic processing by wild-type MMP- 1 on a synthetic substrate and collagen I has been compared with that observed for site-directed mutants obtained either by truncating the hinge region (D255-272) or by individually replacing the conserved amino acids Val268, Gly272, and Lys277 of the hinge region with residues observed for the corresponding position in stromelysin-1 (MMP-3), a noncollagenolytic metalloproteinase. The D256-272 mutant has no collagenolytic activity, clearly demonstrating the crucial role of this region for the enzymatic processing of collagen I. However, among various mutants investigated, only Gly272Asp shows a dramatically reduced enzymatic activity both on the synthetic substrate and on collagen I. This effect, however, is clearly related to the substituting residue, since substitution of Ala or Asn for Gly272 does not have any effect on the kinetic properties of MMP-1. These data suggest that the substrate specificity of MMP-1 is dictated by the reciprocal structural relationships between the catalytic domain and the carboxyterminal domain through the conformational arrangement of the hinge region.

Original languageEnglish (US)
Pages (from-to)663-672
Number of pages10
JournalJournal of Biological Inorganic Chemistry
Volume17
Issue number4
DOIs
StatePublished - Apr 1 2012

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Hinges
Matrix Metalloproteinases
Catalytic Domain
Collagen
Substrates
Processing
Matrix Metalloproteinase 3
Matrix Metalloproteinase 1
Metalloproteases
Substrate Specificity
Collagen Type I
Substitution reactions
Amino Acids
Kinetics

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Inorganic Chemistry

Cite this

The collagenolytic action of MMP-1 is regulated by the interaction between the catalytic domain and the hinge region 1Giovanni Francesco Fasciglione. / Gioia, Magda; Tsukada, Hiroki; Liang, Jian; Iundusi, Riccardo; Tarantino, Umberto; Coletta, Massimo; Pourmotabbed, Tayebeh; Marini, Stefano.

In: Journal of Biological Inorganic Chemistry, Vol. 17, No. 4, 01.04.2012, p. 663-672.

Research output: Contribution to journalArticle

Gioia, Magda ; Tsukada, Hiroki ; Liang, Jian ; Iundusi, Riccardo ; Tarantino, Umberto ; Coletta, Massimo ; Pourmotabbed, Tayebeh ; Marini, Stefano. / The collagenolytic action of MMP-1 is regulated by the interaction between the catalytic domain and the hinge region 1Giovanni Francesco Fasciglione. In: Journal of Biological Inorganic Chemistry. 2012 ; Vol. 17, No. 4. pp. 663-672.
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