The second type II module from human matrix metalloproteinase 2: structure, function and dynamics

Background: Matrix metalloproteinase 2 (MMP-2, gelatinase A, 72 kDa type IV collagenase) has an important role in extracellular matrix degradation dur ing cell migration and tissue remodeling. It is involved in development, in flammation, wound healing, tumor invasion, metastasis and other physiologic al and pathological processes. The enzyme cleaves several types of collagen , elastin, fibronectin and laminin. Binding to collagen is mediated by thre e repeats homologous to fibronectin type II modules, which are inserted in the catalytic domain in proximity to the active site. Results: We have determined the NMR solution structure of the second type I I module from human MMP-P (col-2). The module exhibits a typical type II fo ld with two short double-stranded antiparallel beta sheets and three targe loops packed around a cluster of conserved aromatic residues. Backbone amid e dynamics, derived from N-15 relaxation experiments, correlate well with s olvent accessibility and intramolecular hydrogen bonding. A synthetic pepti de with the collagen consensus sequence, (Pro-Pro-Gly)(6), is shown to inte ract with the module. Conclusions: Spectral perturbations induced by (Pro-Pro-Gly)(6) binding rev eal the region involved in the interaction of col-2 with collagen. The bind ing surface comprises exposed aromatic residues Phe21, Tyr38, Trp40, Tyr47, Tyr53 and Phe55, and the neighboring Gly33-Gly37 segment.