2c6j

From Proteopedia

Revision as of 06:54, 21 November 2007

STRUCTURE OF P. KNOWLESI DBL DOMAIN CAPABLE OF BINDING HUMAN DUFFY ANTIGEN

Overview

Molecular processes that govern pathogenic features of erythrocyte, invasion and cytoadherence in malaria are reliant on Plasmodium-specific, Duffy-binding-like domains (DBLs). These cysteine-rich modules recognize, diverse host cell-surface receptors during pathogenesis. DBLs of parasite, erythrocyte-binding proteins mediate invasion, and those from the, antigenically variant P. falciparum erythrocyte membrane protein 1, (PfEMP1) have been implicated in cytoadherence. The simian and human, malarial parasites, P. knowlesi and P. vivax, invade human erythrocytes, exclusively through the host DARC receptor (Duffy antigen receptor for, chemokines). Here we present the crystal structure of the P. knowlesi DBL, domain (Pkalpha-DBL), which binds to DARC during invasion of human, erythrocytes. Pkalpha-DBL retains the overall fold observed in DBLs from, P. falciparum erythrocyte-binding antigen (EBA)-175 (ref. 4). Mapping the, residues that have previously been implicated in binding highlights a, fairly flat but exposed site for DARC recognition in subdomain 2 of, Pkalpha-DBL; this is in sharp contrast to receptor recognition by EBA-175, (ref. 4). In Pkalpha-DBL, the residues that contact DARC and the clusters, of residues under immune pressure map to opposite surfaces of the DBL, and, suggest a possible mechanism for immune evasion by P. vivax. Our, comparative structural analysis of Pkalpha-DBL and P. falciparum EBA-175, provides a framework for the understanding of malaria parasite DBLs, and, may affect the development of new prophylactic and therapeutic strategies.

About this Structure

2C6J is a Single protein structure of sequence from Plasmodium knowlesi. Full crystallographic information is available from OCA.

Reference

Structural basis for Duffy recognition by the malaria parasite Duffy-binding-like domain., Singh SK, Hora R, Belrhali H, Chitnis CE, Sharma A, Nature. 2006 Feb 9;439(7077):741-4. Epub 2005 Dec 21. PMID:16372020

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