Biology Reference
In-Depth Information
Chapter 6
Structural Basis of Extracellular Matrix
Interactions with Matrix Metalloproteinases
Steven R. Van Doren
Abstract Interactions of the extracellular matrix (ECM) with domains of matrix
metalloproteinases (MMPs) increase their proteolytic action upon matrix compo-
nents. This occurs by multiple structural means. The activating interactions of a
partner protein with pro-MMP-9 and of GAGs with pro-MMP-7 were reported. The
interactions of fibrillar proteins with catalytic domains can traverse the breadth of
the active site cleft and overflow into a neighboring exosite and perhaps beyond.
Exosite interactions bear some resemblance to precedents in thrombin complexes.
Basket-shaped surfaces on fibronectin II-like modules (inserted into the catalytic
domains of MMP-2 and -9) appear to bind protein fibrils, may bend them, and
certainly unwind triple helices. C-terminal hemopexin domains are joined loosely
to the catalytic domain, which might facilitate positioning and movement across
collagen triple helices. At least the first blade of the
-propeller of the hemopexin
domain of MMP-1 seems to interact with the triple helix. Unifying themes among
diverse interactions of MMPs with ECM polymers are (1) that two domains of the
MMP often participate and (2) that the interaction guides the MMP to the site for
proteolytic action.
b
Abbreviations
CBD
Collagen-binding domain composed of three FnII-like modules
CS
Chondroitin sulfate
ECM
Extracellular matrix
FnI
Fibronectin type I
FnII
Fibronectin type II
S.R. Van Doren
Biochemistry Department, University of Missouri, 117 Schweitzer Hall, Columbia, MO
65211, USA
e-mail: vandorens@missouri.edu
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