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Bilayer Membrane Modulation of Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) Structure and Proteolytic Activity

Title: Bilayer Membrane Modulation of Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) Structure and Proteolytic Activity.
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Name(s): Cerofolini, Linda, author
Amar, Sabrina, author
Lauer, Janelle L., author
Martelli, Tommaso, author
Fragai, Marco, author
Luchinat, Claudio, author
Fields, Gregg B., author
Type of Resource: text
Genre: Article
Date Issued: 2016-09-13
Abstract: Cell surface proteolysis is an integral yet poorly understood physiological process. The present study has examined how the pericellular collagenase membrane-type 1 matrix metalloproteinase (MT1-MMP) and membrane-mimicking environments interplay in substrate binding and processing. NMR derived structural models indicate that MT1-MMP transiently associates with bicelles and cells through distinct residues in blades III and IV of its hemopexin-like domain, while binding of collagen-like triple-helices occurs within blades I and II of this domain. Examination of simultaneous membrane interaction and triple-helix binding revealed a possible regulation of proteolysis due to steric effects of the membrane. At bicelle concentrations of 1%, enzymatic activity towards triple-helices was increased 1.5-fold. A single mutation in the putative membrane interaction region of MT1-MMP (Ser466Pro) resulted in lower enzyme activation by bicelles. An initial structural framework has thus been developed to define the role(s) of cell membranes in modulating proteolysis.
Identifier: 10.1038/srep29511 (doi), http://www.nature.com/articles/srep29511 (uri), FAUIR0000004 (IID)
Persistent Link to This Record: http://purl.flvc.org/fau/fd/FAUIR0000004
Use and Reproduction: publisher
Owner Institution: FAU
Is Part Of: Scientific Reports.
2045-2322