|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 95 No. 11 (June 1), 2000:
pp. 3594-3599
The Duffy-binding-like domain 1 of Plasmodium falciparum
erythrocyte membrane protein 1 (PfEMP1) is a heparan sulfate
ligand that requires 12 mers for binding
Antonio Barragan,
Victor Fernandez,
Qijun Chen,
Anne von Euler,
Mats Wahlgren, and
Dorothe Spillmann
From the Microbiology and Tumor Biology Center, Karolinska
Institutet and Swedish Institute for Infectious Disease Control,
Stockholm, and the Department of Medical Biochemistry and Microbiology,
Uppsala University, Biomedical Center, Uppsala, Sweden.
The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), present on the surfaces of parasitized red blood cells (pRBC), mediates rosetting, a virulent phenotype. Here, we show that
pRBC specifically bind heparan sulfate (HS) and heparin onto their
surfaces and that the rosetting ligand PfEMP1 specifically adheres to
heparin-Sepharose when extracted from the surfaces of radioiodinated
infected RBC. An analysis of the binding properties of the different
regions of PfEMP1 provides evidence that the Duffy-binding-like
domain-1 (DBL-1) is the predominant ligand involved in HS and heparin
binding. Soluble DBL-1 requires a minimal heparin fragment size of a
12-mer ( 4 kd) for binding and is critically dependent on N-sulfation. A 12-mer is also the minimal heparin fragment that disrupts naturally formed rosettes. DBL-1 binds specifically to erythrocytes and also to HS from endothelial
cells and human aorta but not to chondroitin sulfate A,
suggesting that different PfEMP1s mediate adhesion to distinct
glycosaminoglycans in individual malaria parasites. Present data
suggest that HS on endothelial cells may also be involved in the
sequestration of pRBC. Elucidation of these binding mechanisms opens up
new possibilities for therapeutic strategies targeting adhesive
interactions of pRBC.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
D. R. Krause, M. L. Gatton, S. Frankland, D. P. Eisen, M. F. Good, L. Tilley, and Q. Cheng
Characterization of the Antibody Response against Plasmodium falciparum Erythrocyte Membrane Protein 1 in Human Volunteers
Infect. Immun.,
December 1, 2007;
75(12):
5967 - 5973.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Mayor, N. Bir, R. Sawhney, S. Singh, P. Pattnaik, S. K. Singh, A. Sharma, and C. E. Chitnis
Receptor-binding residues lie in central regions of Duffy-binding-like domains involved in red cell invasion and cytoadherence by malaria parasites
Blood,
March 15, 2005;
105(6):
2557 - 2563.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Bork, N. Yokoyama, Y. Ikehara, S. Kumar, C. Sugimoto, and I. Igarashi
Growth-Inhibitory Effect of Heparin on Babesia Parasites
Antimicrob. Agents Chemother.,
January 1, 2004;
48(1):
236 - 241.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Vogt, A. Barragan, Q. Chen, F. Kironde, D. Spillmann, and M. Wahlgren
Heparan sulfate on endothelial cells mediates the binding of Plasmodium falciparum-infected erythrocytes via the DBL1alpha domain of PfEMP1
Blood,
March 15, 2003;
101(6):
2405 - 2411.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Kisilevsky, I. Crandall, W. A. Szarek, S. Bhat, C. Tan, L. Boudreau, and K. C. Kain
Short-Chain Aliphatic Polysulfonates Inhibit the Entry of Plasmodium into Red Blood Cells
Antimicrob. Agents Chemother.,
August 1, 2002;
46(8):
2619 - 2626.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Chai, J. G. Beeson, and A. M. Lawson
The Structural Motif in Chondroitin Sulfate for Adhesion of Plasmodium falciparum-infected Erythrocytes Comprises Disaccharide Units of 4-O-Sulfated and Non-sulfated N-Acetylgalactosamine Linked to Glucuronic Acid
J. Biol. Chem.,
June 14, 2002;
277(25):
22438 - 22446.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Heddini, F. Pettersson, O. Kai, J. Shafi, J. Obiero, Q. Chen, A. Barragan, M. Wahlgren, and K. Marsh
Fresh Isolates from Children with Severe Plasmodium falciparum Malaria Bind to Multiple Receptors
Infect. Immun.,
September 1, 2001;
69(9):
5849 - 5856.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Chai, J. G. Beeson, H. Kogelberg, G. V. Brown, and A. M. Lawson
Inhibition of Adhesion of Plasmodium falciparum-Infected Erythrocytes by Structurally Defined Hyaluronic Acid Dodecasaccharides
Infect. Immun.,
January 1, 2001;
69(1):
420 - 425.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
