Extracellular matrix remodeling and vascular complications in type1 diabetes

Abstract

The general protein structure of MMPs is shown in Figure 1.1. MMPs consist of three main parts: the N-terminal propeptide, the C-terminal (hemopexin-like) domain and the catalytic domain. 52-54 Cystein is the most important amino acid in the propeptide domain and is connected with the Zn 2+-ions in the catalytic domain. Removal of this connection activates the proMMP. The C-terminal domain is necessary for protein-protein interactions, e.g. with matrix components or with its inhibitor, tissue inhibitor of metalloproteinase (TIMP). The catalytic domain contains two Zn 2+-ions and two or three Ca 2+-ions. The first Zn 2+-ion is involved in the catalytic function, while Ca 2+-ions are necessary for stabilizing the catalytic domain structure. Besides these domains all MMPs, except MMP-23A and B, contain a signal peptide needed for secretion. Membraneassociated MMPs are anchored through glycosylphosphatidylinositol (GPI) or transmembrane segments I or II (TMI or TMII). In addition, specific binding sites (Figure 1.1: Y, D and G) characterize the different collagenases and specific fibronectin type II molecules are present in MMP-2 and MMP-9, which improve gelatin and collagen degradation.