Receptor-binding residues lie in central regions of duffy-binding-like domains involved in red cell invasion and cytoadherence by malaria parasites

Mayor, Alfredo ; Bir, Nivedita ; Sawhney, Ritica ; Singh, Shailja ; Pattnaik, Priyabrata ; Singh, Saurabh Kumar ; Sharma, Amit ; Chitnis, Chetan E. (2005) Receptor-binding residues lie in central regions of duffy-binding-like domains involved in red cell invasion and cytoadherence by malaria parasites Blood, 105 (6). pp. 2557-2563. ISSN 0006-4971

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Official URL: http://bloodjournal.hematologylibrary.org/cgi/cont...

Related URL: http://dx.doi.org/10.1182/blood-2004-05-1722

Abstract

Erythrocyte invasion by malaria parasites and cytoadherence of Plasmodium falciparum-infected erythrocytes to host capillaries are 2 key pathogenic mechanisms in malaria. The receptor-binding domains of erythrocyte-binding proteins (EBPs) such as Plasmodium falciparum EBA-175, which mediate invasion, and P falciparum erythrocyte membrane protein 1 (PfEMP-1) family members, which are encoded by var genes and mediate cytoadherence, have been mapped to conserved cysteine-rich domains referred to as Duffy-binding-like (DBL) domains. Here, we have mapped regions within DBL domains from EBPs and PfEMP-1 that contain receptor-binding residues. Using biochemical and molecular methods we demonstrate that the receptor-binding residues of parasite ligands that bind sialic acid on glycophorin A for invasion as well as complement receptor-1 and chondroitin sulfate A for cytoadherence map to central regions of DBL domains. In contrast, binding to intercellular adhesion molecule 1 (ICAM-1) requires both the central and terminal regions of DBLβC2 domains. Determination of functional regions within DBL domains is the first step toward understanding the structure-function bases for their interaction with diverse host receptors.

Item Type:Article
Source:Copyright of this article belongs to American Society of Hematology.
ID Code:5574
Deposited On:19 Oct 2010 11:52
Last Modified:16 May 2016 16:03

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