Interdomain Flexibility in Full-length Matrix Metalloproteinase-1 (MMP-1)

Ivano Bertini,Marco Fragai,Claudio Luchinat,Maxime Melikian,Efstratios Mylonas,Niko Sarti,Dmitri I Svergun

doi:10.1074/jbc.m809627200

Abstract

The presence of extensive reciprocal conformational freedom between the catalytic and the hemopexin-like domains of full-length matrix metalloproteinase-1 (MMP-1) is demonstrated by NMR and small angle x-ray scattering experiments. This finding is discussed in relation to the essentiality of the hemopexin-like domain for the collagenolytic activity of MMP-1. The conformational freedom experienced by the present system, having the shortest linker between the two domains, when compared with similar findings on MMP-12 and MMP-9 having longer and the longest linker within the family, respectively, suggests this type of conformational freedom to be a general property of all MMPs.

Highlights

All Matrix metalloproteinases (MMP) in their active form are constituted by a catalytic domain (CAT) and a hemopexin-like domain (HPX) (20 –22)
When needed, cadmium(II) was substituted for zinc(II) in the catalytic site to further reduce the residual activity as it was already shown for FL-MMP-12 and its CAT domain [34]. 15N, 13C15N, and 2H-13C-15N-enriched samples were used for NMR investigations
Concluding Remarks and Biological Implications—The present data demonstrate that FL-matrix metalloproteinase-1 (MMP-1) shows relative mobility of its catalytic and hemopexin-like domains, as recently observed for FL-MMP-12 [34]

Summary

Introduction

All MMPs (but MMP-7) in their active form are constituted by a catalytic domain (CAT) and a hemopexin-like domain (HPX) (20 –22). The presence of extensive reciprocal conformational freedom between the catalytic and the hemopexin-like domains of fulllength matrix metalloproteinase-1 (MMP-1) is demonstrated by NMR and small angle x-ray scattering experiments.

Results

Conclusion