Sequence similarity between the erythrocyte binding domain of the Plasmodium vivax Duffy binding protein and the V3 loop of HIV-1 strain MN reveals a functional heparin binding motif involved in binding to the Duffy antigen receptor for chemokines.

Abstract

BACKGROUND:

The HIV surface glycoprotein gp120 (SU, gp120) and the Plasmodium vivax Duffy binding protein (PvDBP) bind to chemokine receptors during infection and have a site of amino acid sequence similarity in their binding domains that often includes a heparin binding motif (HBM). Infection by either pathogen has been found to be inhibited by polyanions.

RESULTS:

Specific polyanions that inhibit HIV infection and bind to the V3 loop of X4 strains also inhibited DBP-mediated infection of erythrocytes and DBP binding to the Duffy Antigen Receptor for Chemokines (DARC). A peptide including the HBM of PvDBP had similar affinity for heparin as RANTES and V3 loop peptides, and could be specifically inhibited from heparin binding by the same polyanions that inhibit DBP binding to DARC. However, some V3 peptides can competitively inhibit RANTES binding to heparin, but not the PvDBP HBM peptide. Three other members of the DBP family have an HBM sequence that is necessary for erythrocyte binding, however only the protein which binds to DARC, the P. knowlesi alpha protein, is inhibited by heparin from binding to erythrocytes. Heparitinase digestion does not affect the binding of DBP to erythrocytes.

CONCLUSION:

The HBMs of DBPs that bind to DARC have similar heparin binding affinities as some V3 loop peptides and chemokines, are responsible for specific sulfated polysaccharide inhibition of parasite binding and invasion of red blood cells, and are more likely to bind to negative charges on the receptor than cell surface glycosaminoglycans.

• Authors: Michael J Bolton, Robert F Garry
• Journal: Virology journal (Virol J) Vol. 8 Pg. 523 (Nov 28 2011) ISSN: 1743-422X [Electronic] England
• PMID: 22122911 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• ACKR1 protein, human
• Anti-HIV Agents
• Antigens, Protozoan
• Antimalarials
• Duffy Blood-Group System
• Duffy antigen binding protein, Plasmodium
• HIV Envelope Protein gp120
• Polyelectrolytes
• Polymers
• Protozoan Proteins
• Receptors, Cell Surface
• gp120 protein, Human immunodeficiency virus 1
• polyanions
• Heparin

Topics

• Amino Acid Sequence
• Anti-HIV Agents (metabolism)
• Antigens, Protozoan (genetics)
• Antimalarials (metabolism)
• Binding Sites
• Duffy Blood-Group System (metabolism)
• Erythrocytes (parasitology)
• HIV Envelope Protein gp120 (genetics)
• Heparin (metabolism)
• Humans
• Molecular Sequence Data
• Plasmodium knowlesi (genetics, pathogenicity)
• Plasmodium vivax (genetics, pathogenicity)
• Polyelectrolytes
• Polymers (metabolism)
• Protein Binding
• Protozoan Proteins (genetics)
• Receptors, Cell Surface (genetics, metabolism)
• Sequence Homology, Amino Acid