| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 276, Issue 29, 27613-27621, July 20, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Human matrix metalloproteinase-2 (MMP-2) contains
an array of three fibronectin type II (FII) modules postulated to
interact with gelatin (denatured collagen). Here, we verify that the
NMR solution structure of the third FII repeat (COL-3) is similar to
that of the second FII repeat (COL-2); characterize its ligand-binding properties; and derive dynamics properties and relative orientation in
solution for the two domains of the COL-23 fragment, a construct comprising COL-2 and COL-3 in tandem, with each domain possessing a
putative collagen-binding site. Interaction of the synthetic gelatin-like octadecapeptide (Pro-Pro-Gly)6 (PPG6) with
COL-3 is weaker than with COL-2. We found that a synthetic peptide
comprising segment 33-42 (peptide 33-42) from the MMP-2 prodomain
interacts with COL-3 and, albeit with lower affinity, with COL-2 in a
way that mimics PPG6 binding. COL-3 strongly prefers peptide 33-42 over PPG6, which suggests that intramolecular interactions with the
prodomain could modulate binding of pro-MMP-2 to its gelatin substrate.
In COL-23, the two modules retain their structural individuality and
tumble independently. Overall, the NMR data indicate that the relative
orientation of the modules in COL-23 is not fixed in solution, that the
modules do not interact with one another, and that COL-23 is rather
flexible. The binding sites face opposite each other, and their
responses to, and normalized affinities for, the longer ligand PPG12
are virtually identical to those of the individual domains for
PPG6, thus precluding co- operativity, although they may interact
simultaneously with multiple sites of the extracellular matrix.
Gelatin-binding Region of Human Matrix Metalloproteinase-2
SOLUTION STRUCTURE, DYNAMICS, AND FUNCTION OF THE COL-23
TWO-DOMAIN CONSTRUCT*,
§,,
Department of Chemistry, Carnegie Mellon
University, Pittsburgh, Pennsylvania 15213 and the ¶ Institute of
Enzymology, Biological Research Center, Hungarian Academy of Sciences,
Budapest H-1518, Hungary
*
This work was supported by National Institutes of Health
Grant HL29409, International Center for Genetic Engineering and
Biotechnology (Trieste) Grant CRP/HUN98-03, and National
Scientific Research Programs of Hungary (OTKA) Grant T0022949.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
The on-line version of this article (available at
http://www.jbc.org) contains Supplemental Tables I and II.
The atomic coordinates and NMR constraints (code 1J7M) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).
NMR chemical shifts have been deposited in the BioMagResBank Database under BMRB accession number 4126.
§ Present address: Burnham Inst., 10901 North Torrey Pines Rd., La Jolla, CA 92037.
To whom correspondence should be addressed: Dept. of
Chemistry, Carnegie Mellon University, 4400 Fifth Ave., Pittsburgh, PA 15213. Tel.: 412-268-3140; Fax: 412-268-1061; E-mail:
llinas+@andrew.cmu.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Nagase, R. Visse, and G. Murphy Structure and function of matrix metalloproteinases and TIMPs Cardiovasc Res, February 15, 2006; 69(3): 562 - 573. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Gehrmann, J. T. Douglas, L. Banyai, H. Tordai, L. Patthy, and M. Llinas Modular Autonomy, Ligand Specificity, and Functional Cooperativity of the Three In-tandem Fibronectin Type II Repeats from Human Matrix Metalloproteinase 2 J. Biol. Chem., November 5, 2004; 279(45): 46921 - 46929. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Tam, T. R. Moore, G. S. Butler, and C. M. Overall Characterization of the Distinct Collagen Binding, Helicase and Cleavage Mechanisms of Matrix Metalloproteinase 2 and 14 (Gelatinase A and MT1-MMP): THE DIFFERENTIAL ROLES OF THE MMP HEMOPEXIN C DOMAINS AND THE MMP-2 FIBRONECTIN TYPE II MODULES IN COLLAGEN TRIPLE HELICASE ACTIVITIES J. Biol. Chem., October 8, 2004; 279(41): 43336 - 43344. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. R.F. Mook, C. Van Overbeek, E. G. Ackema, F. Van Maldegem, and W. M. Frederiks In Situ Localization of Gelatinolytic Activity in the Extracellular Matrix of Metastases of Colon Cancer in Rat Liver Using Quenched Fluorogenic DQ-gelatin J. Histochem. Cytochem., June 1, 2003; 51(6): 821 - 829. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Visse and H. Nagase Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases: Structure, Function, and Biochemistry Circ. Res., May 2, 2003; 92(8): 827 - 839. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Trexler, K. Briknarova, M. Gehrmann, M. Llinas, and L. Patthy Peptide Ligands for the Fibronectin Type II Modules of Matrix Metalloproteinase 2 (MMP-2) J. Biol. Chem., March 28, 2003; 278(14): 12241 - 12246. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
