2mzi
NMR Solution Structure of the PRO Form of Human Matrilysin (proMMP-7) in Complex with Anionic Membrane
Structural highlights
FunctionMMP7_HUMAN Degrades casein, gelatins of types I, III, IV, and V, and fibronectin. Activates procollagenase.[1] Publication Abstract from PubMedMatrix metalloproteinase-7 (MMP-7) sheds signaling proteins from cell surfaces to activate bacterial killing, wound healing, and tumorigenesis. The mechanism targeting soluble MMP-7 to membranes has been investigated. Nuclear magnetic resonance structures of the zymogen, free and bound to membrane mimics without and with anionic lipid, reveal peripheral binding to bilayers through paramagnetic relaxation enhancements. Addition of cholesterol sulfate partially embeds the protease in the bilayer, restricts its diffusion, and tips the active site away from the bilayer. Its insertion of hydrophobic residues organizes the lipids, pushing the head groups and sterol sulfate outward toward the enzyme's positive charge on the periphery of the enlarged interface. Fluorescence probing demonstrates a similar mode of binding to plasma membranes and internalized vesicles of colon cancer cells. Binding of bilayered micelles induces allosteric activation and conformational change in the auto-inhibitory peptide and the adjacent scissile site, illustrating a potential intermediate in the activation of the zymogen. Charge-Triggered Membrane Insertion of Matrix Metalloproteinase-7, Supporter of Innate Immunity and Tumors.,Prior SH, Fulcher YG, Koppisetti RK, Jurkevich A, Van Doren SR Structure. 2015 Nov 3;23(11):2099-110. doi: 10.1016/j.str.2015.08.013. Epub 2015 , Oct 1. PMID:26439767[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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