| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 275, Issue 35, 26799-26805, September 1, 2000
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Protein Engineering Network of Centers of Excellence and
the Department of Biochemistry, 713 Heritage Medical Research Center,
University of Alberta, Edmonton, Alberta T6G 2S2, Canada
Stromal cell-derived factor 1 (SDF-1), a member
of the CXC chemokine family, is the only chemokine to bind to the
receptor CXCR4. This receptor is also a co-receptor for
syncytia-inducing forms of HIV in CD4+ cells. In
addition, SDF-1 is responsible for attracting mature lymphocytes to the
bone marrow and can therefore contribute to host versus
graft rejection in bone marrow transplantation. Clearly, by
manipulating SDF-1 activity, we could find a possible anti-viral AIDS
treatment and aid in bone marrow transplantation. SDF-1 binds to CXCR4
primarily via the N terminus, which appears flexible in the recently
determined three-dimensional structure of SDF-1. Strikingly, short
N-terminal SDF-1 peptides have been shown to have significant SDF-1
activity. By using NMR, we have determined the major conformation of
the N terminus of SDF-1 in a 17-mer (residues 1-17 of SDF-1) and a
9-mer dimer (residues 1-9 of SDF-1 linked by a disulfide bond at
residue 9). Residues 5-8 and 11-14 form similar structures that can
be characterized as a
NMR Studies of Active N-terminal Peptides of Stromal Cell-derived
Factor-1
STRUCTURAL BASIS FOR RECEPTOR BINDING*
,,
-turn of the -
R type. These structural
motifs are likely to be interconverting with other states, but the
major conformation may be important for recognition in receptor
binding. These results suggest for the first time that there may be a
link between structuring of short N-terminal chemokine peptides and
their ability to activate their receptor. These studies will act as a
starting point for synthesizing non-peptide analogs that act as CXCR4 antagonists.
*
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.
These authors contributed equally to this work.
§
Present address: Dept. of Biochemistry and Molecular Biology,
University of Southampton, Bassett Crescent East, Southampton, SO16
7PX, UK.
¶
Present address: Biomedical Research Centre, University of
British Columbia, 2222 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
To whom correspondence should be addressed. Tel.:
780-492-6540; Fax: 780-492-1473; E-mail:
brian.sykes@ualberta.ca.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  P. Sathyanarayana, M. P. Menon, O. Bogacheva, O. Bogachev, K. Niss, W. S. Kapelle, E. Houde, J. Fang, and D. M. Wojchowski Erythropoietin modulation of podocalyxin and a proposed erythroblast niche Blood, July 15, 2007; 110(2): 509 - 518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-B. Huang, L. L. Jin, C. O. James, M. Khan, M. D. Powell, and V. C. Bond Characterization of Nef-CXCR4 Interactions Important for Apoptosis Induction J. Virol., October 15, 2004; 78(20): 11084 - 11096. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Huang, J. Shen, M. Cui, L. Shen, X. Luo, K. Ling, G. Pei, H. Jiang, and K. Chen Molecular Dynamics Simulations on SDF-1{alpha}: Binding with CXCR4 Receptor Biophys. J., January 1, 2003; 84(1): 171 - 184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Braun, M. Wunderlin, K. Spieth, W. Knochel, P. Gierschik, and B. Moepps Xenopus laevis Stromal Cell-Derived Factor 1: Conservation of Structure and Function During Vertebrate Development J. Immunol., March 1, 2002; 168(5): 2340 - 2347. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. T. Seet, R. Singh, C. Paavola, E. K. Lau, T. M. Handel, and G. McFadden Molecular determinants for CC-chemokine recognition by a poxvirus CC-chemokine inhibitor PNAS, July 19, 2001; (2001) 171069398. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Loetscher and I. Clark-Lewis Agonistic and antagonistic activities of chemokines J. Leukoc. Biol., June 1, 2001; 69(6): 881 - 884. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Sadir, F. Baleux, A. Grosdidier, A. Imberty, and H. Lortat-Jacob Characterization of the Stromal Cell-derived Factor-1alpha -Heparin Complex J. Biol. Chem., March 9, 2001; 276(11): 8288 - 8296. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. S. Mizoue, S. K. Sullivan, D. S. King, T. N. Kledal, T. W. Schwartz, K. B. Bacon, and T. M. Handel Molecular Determinants of Receptor Binding and Signaling by the CX3C Chemokine Fractalkine J. Biol. Chem., August 31, 2001; 276(36): 33906 - 33914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. T. Seet, R. Singh, C. Paavola, E. K. Lau, T. M. Handel, and G. McFadden Molecular determinants for CC-chemokine recognition by a poxvirus CC-chemokine inhibitor PNAS, July 31, 2001; 98(16): 9008 - 9013. [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 |
