The col-1 module of human matrix metalloproteinase-2 (MMP-2): structural/functional relatedness between gelatin-binding fibronectin type II modules and lysine-binding kringle domains

Biological Chemistry
Marion L GehrmannM Llinás

Abstract

Human matrix metalloproteinase-2 (MMP-2) contains three in-tandem fibronectin type II (FII) repeats that bind gelatin. Here, we report the NMR solution structure of the first FII module of MMP-2 (col-1). The latter is described as a characteristic, globular FII fold containing two beta-sheets, a stretch of 3(1)-helix, a turn of alpha-helix, and an exposed hydrophobic surface lined with aromatic residues. We show that col-1 binds (Pro-Pro-Gly)6, a mimic of gelatin, with a Ka of approx. 0.42 mm(-1), and that its binding site involves a number of aromatic residues as well as Arg34, as previously found for the second and third homologous repeats. Moreover, the affinity of the in-tandem col-1+2 construct (col-12) toward the longer ligand (Pro-Pro-Gly)12 is twice that for (Pro-Pro-Gly)6, as expected from mass action. A detailed structural comparison between FII and kringle domains indicates that four main conformational features are shared: two antiparallel beta-sheets, a central 3(1)-helix, and the quasiperpendicular orientation of the two proximal Cys-Cys bonds. Structure superposition by optimizing overlap of cystine bridge areas results in close juxtaposition of their main beta-sheets and 31-helices, and reveals that the gelatin ...Continue Reading

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Citations

Oct 23, 2012·Matrix Biology : Journal of the International Society for Matrix Biology·Margarita MikhailovaBjorn Steffensen
Feb 20, 2007·Gene·Mahnaz Ekhlasi-HundrieserEdda Töpfer-Petersen
Aug 9, 2005·Pathologie-biologie·W HornebeckH Emonard
May 24, 2005·Biochimica Et Biophysica Acta·Mikael Björklund, Erkki Koivunen
Jan 21, 2015·Matrix Biology : Journal of the International Society for Matrix Biology·Steven R Van Doren
Jun 16, 2009·Journal of Structural Biology·Olga A Ozhogina, Emile L Bominaar
Mar 23, 2005·Biochimie·Márton JaniLászló Patthy
Dec 18, 2002·The Journal of Biological Chemistry·Maria TrexlerLászló Patthy
Jun 13, 2020·Critical Reviews in Biochemistry and Molecular Biology·Andrea Heinz
Jun 17, 2021·The Protein Journal·Manuel Llinás

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