Trexler Maria, Briknarová Klára, Gehrmann Marion, Llinás Miguel, Patthy László
Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, Budapest H-1518, Hungary.
J Biol Chem. 2003 Apr 4;278(14):12241-6. doi: 10.1074/jbc.M210116200. Epub 2002 Dec 16.
The interaction of matrix metalloproteinase 2 (MMP-2) with gelatin is mediated by three repeats homologous to fibronectin type II (FN2) modules, which are inserted in the catalytic domain in proximity of the active site. We screened a random 15-mer phage display library to identify peptides that interact with the FN2 modules of MMP-2. Interestingly, the selected peptides are not gelatin-like and do not share a common, obvious sequence motif. However, they contain a high proportion of aromatic residues. The interactions of two peptides, WHWRH0RIPLQLAAGR and THSHQWRHHQFPAPT, with constructs comprising the in-tandem first and second and second and third FN2 modules of MMP-2 (Col-12 and Col-23, respectively) were characterized by NMR. Both peptides interact with Col-12 and Col-23 with apparent association constants in the mm(-1) range. Peptide binding results in perturbation of signals from residues located in the gelatin-binding pocket and flexible parts of the molecule. Although the former finding suggests that the gelatin-binding site is involved in the contact, the interpretation of the latter is less straightforward and may well reflect both the direct and indirect effects of the interaction.
基质金属蛋白酶2（MMP-2）与明胶的相互作用由三个与纤连蛋白II型（FN2）模块同源的重复序列介导，这些重复序列插入到靠近活性位点的催化结构域中。我们筛选了一个随机的15肽噬菌体展示文库，以鉴定与MMP-2的FN2模块相互作用的肽段。有趣的是，所选肽段不像明胶，也没有共同的明显序列基序。然而，它们含有高比例的芳香族残基。通过核磁共振（NMR）对两个肽段WHWRH0RIPLQLAAGR和THSHQWRHHQFPAPT与包含MMP-2串联的第一和第二个以及第二和第三个FN2模块的构建体（分别为Col-12和Col-23）的相互作用进行了表征。两个肽段与Col-12和Col-23相互作用，表观缔合常数在mm⁻¹范围内。肽段结合导致位于明胶结合口袋和分子柔性部分的残基信号发生扰动。虽然前一个发现表明明胶结合位点参与了接触，但后一个发现的解释不太直接，很可能反映了相互作用的直接和间接影响。
