Structural Basis for Inhibition of Erythrocyte Invasion by Antibodies to Protein CyRPA

Overview

Journal Elife

Specialty Biology

Date 2017 Feb 15

PMID 28195530

Citations 32

Authors

Lin Chen

Yibin Xu

Wilson Wong

Jennifer K Thompson

Julie Healer

Ethan D Goddard-Borger

Michael C Lawrence

Alan F Cowman

Affiliations

Soon will be listed here.

Abstract

causes malaria in humans with over 450,000 deaths annually. The asexual blood stage involves invasion of erythrocytes by merozoites, in which they grow and divide to release daughter merozoites, which in turn invade new erythrocytes perpetuating the cycle responsible for malaria. A key step in merozoite invasion is the essential binding of PfRh5/CyRPA/PfRipr complex to basigin, a step linked to the formation of a pore between merozoites and erythrocytes. We show CyRPA interacts directly with PfRh5. An invasion inhibitory monoclonal antibody to CyRPA blocks binding of CyRPA to PfRh5 and complex formation thus illuminating the molecular mechanism for inhibition of parasite growth. We determined the crystal structures of CyRPA alone and in complex with an antibody Fab fragment. CyRPA has a six-bladed β-propeller fold, and we identify the region that interacts with PfRh5. This functionally conserved epitope is a potential target for vaccines against .

Citing Articles

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