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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.
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.
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