Biophysical studies of matrix metalloproteinase/triple-helix complexes

Adv Protein Chem Struct Biol. 2014:97:37-48. doi: 10.1016/bs.apcsb.2014.09.001. Epub 2014 Nov 7.

Abstract

Several members of the zinc-dependent matrix metalloproteinase (MMP) family catalyze collagen degradation. The structures of MMPs, in solution and solid state and in the presence and absence of triple-helical collagen models, have been assessed by NMR spectroscopy, small-angle X-ray scattering, and X-ray crystallography. Structures observed in solution exhibit flexibility between the MMP catalytic (CAT) and hemopexin-like (HPX) domains, while solid-state structures are relatively compact. Evaluation of the maximum occurrence (MO) of MMP-1 conformations in solution found that, for all the high MO conformations, the CAT and HPX domains are not in tight contact, and the residues of the HPX domain reported to be responsible for the binding to the collagen triple-helix are solvent exposed. A mechanism for collagenolysis has been developed based on analysis of MMP solution structures. Information obtained from solid-state structures has proven valuable for analyzing specific contacts between MMPs and the collagen triple-helix.

Keywords: Collagen; Collagenolysis; Matrix metalloproteinase; Maximum occurrence; Proteolysis; Triple-helix.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Catalytic Domain
  • Collagen / chemistry*
  • Humans
  • Hydrolysis
  • Matrix Metalloproteinase 1 / chemistry*
  • Models, Molecular
  • Protein Interaction Domains and Motifs
  • Protein Structure, Secondary
  • Solutions

Substances

  • Solutions
  • Collagen
  • Matrix Metalloproteinase 1