Processing of Plasmodium falciparum merozoite surface protein MSP1 activates a spectrin-binding function enabling parasite egress from RBCs

Das, S. et al. (2015) Processing of Plasmodium falciparum merozoite surface protein MSP1 activates a spectrin-binding function enabling parasite egress from RBCs. Cell Host and Microbe, 18(4), pp. 433-444. (doi: 10.1016/j.chom.2015.09.007) (PMID:26468747) (PMCID:PMC4608996)

Abstract

The malaria parasite Plasmodium falciparum replicates within erythrocytes, producing progeny merozoites that are released from infected cells via a poorly understood process called egress. The most abundant merozoite surface protein, MSP1, is synthesized as a large precursor that undergoes proteolytic maturation by the parasite protease SUB1 just prior to egress. The function of MSP1 and its processing are unknown. Here we show that SUB1-mediated processing of MSP1 is important for parasite viability. Processing modifies the secondary structure of MSP1 and activates its capacity to bind spectrin, a molecular scaffold protein that is the major component of the host erythrocyte cytoskeleton. Parasites expressing an inefficiently processed MSP1 mutant show delayed egress, and merozoites lacking surface-bound MSP1 display a severe egress defect. Our results indicate that interactions between SUB1-processed merozoite surface MSP1 and the spectrin network of the erythrocyte cytoskeleton facilitate host erythrocyte rupture to enable parasite egress.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Das, Dr Sujaan
• Authors: Das, S., Hertrich, N., Perrin, A. J., Withers-Martinez, C., Collins, C. R., Jones, M. L., Watermeyer, J. M., Fobes, E. T., Martin, S. R., Saibil, H. R., Wright, G. J., Treeck, M., Epp, C., and Blackman, M. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Cell Host and Microbe
• Publisher: Elsevier
• ISSN: 1931-3128
• ISSN (Online): 1934-6069
• Published Online: 14 October 2015
• Copyright Holders: Copyright © 2015 The Authors
• First Published: First published in Cell Host and Microbe 18(4):433-444
• Publisher Policy: Reproduced under a Creative Commons License