Processing of Plasmodium falciparum Merozoite Surface Protein MSP1 Activates a Spectrin-Binding Function Enabling Parasite Egress from RBCs

Sujaan Das; Nadine Hertrich; Abigail J Perrin; Chrislaine Withers-Martinez; Christine R Collins; Matthew L Jones; Jean M Watermeyer; Elmar T Fobes; Stephen R Martin; Helen R Saibil; Gavin J Wright; Moritz Treeck; Christian Epp; Michael J Blackman

doi:10.1016/j.chom.2015.09.007

Processing of Plasmodium falciparum Merozoite Surface Protein MSP1 Activates a Spectrin-Binding Function Enabling Parasite Egress from RBCs

Sujaan Das, Nadine Hertrich, Abigail J Perrin, Chrislaine Withers-Martinez, Christine R Collins, Matthew L Jones, Jean M Watermeyer, Elmar T Fobes, Stephen R Martin, Helen R Saibil, Gavin J Wright, Moritz Treeck, Christian Epp, Michael J Blackman

Research output: Contribution to journal › Article › peer-review

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. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Original language	English
Pages (from-to)	433-444
Number of pages	12
Journal	Cell Host & Microbe
Volume	18
Issue number	4
DOIs	https://doi.org/10.1016/j.chom.2015.09.007
Publication status	Published - 14 Oct 2015

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10.1016/j.chom.2015.09.007

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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., & Blackman, M. J. (2015). Processing of Plasmodium falciparum Merozoite Surface Protein MSP1 Activates a Spectrin-Binding Function Enabling Parasite Egress from RBCs. Cell Host & Microbe, 18(4), 433-444. https://doi.org/10.1016/j.chom.2015.09.007

@article{a3098d1df38a4631ad12d229872e9e85,

title = "Processing of Plasmodium falciparum Merozoite Surface Protein MSP1 Activates a Spectrin-Binding Function Enabling Parasite Egress from RBCs",

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. Copyright {\textcopyright} 2015 The Authors. Published by Elsevier Inc. All rights reserved.",

author = "Sujaan Das and Nadine Hertrich and Perrin, {Abigail J} and Chrislaine Withers-Martinez and Collins, {Christine R} and Jones, {Matthew L} and Watermeyer, {Jean M} and Fobes, {Elmar T} and Martin, {Stephen R} and Saibil, {Helen R} and Wright, {Gavin J} and Moritz Treeck and Christian Epp and Blackman, {Michael J}",

year = "2015",

month = oct,

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doi = "10.1016/j.chom.2015.09.007",

language = "English",

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Das, S, Hertrich, N, Perrin, AJ, Withers-Martinez, C, Collins, CR, Jones, ML, Watermeyer, JM, Fobes, ET, Martin, SR, Saibil, HR, Wright, GJ, Treeck, M, Epp, C & Blackman, MJ 2015, 'Processing of Plasmodium falciparum Merozoite Surface Protein MSP1 Activates a Spectrin-Binding Function Enabling Parasite Egress from RBCs', Cell Host & Microbe, vol. 18, no. 4, pp. 433-444. https://doi.org/10.1016/j.chom.2015.09.007

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T1 - Processing of Plasmodium falciparum Merozoite Surface Protein MSP1 Activates a Spectrin-Binding Function Enabling Parasite Egress from RBCs

AU - Das, Sujaan

AU - Hertrich, Nadine

AU - Perrin, Abigail J

AU - Withers-Martinez, Chrislaine

AU - Collins, Christine R

AU - Jones, Matthew L

AU - Watermeyer, Jean M

AU - Fobes, Elmar T

AU - Martin, Stephen R

AU - Saibil, Helen R

AU - Wright, Gavin J

AU - Treeck, Moritz

AU - Epp, Christian

AU - Blackman, Michael J

PY - 2015/10/14

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N2 - 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. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

AB - 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. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

U2 - 10.1016/j.chom.2015.09.007

DO - 10.1016/j.chom.2015.09.007

M3 - Article

SN - 1931-3128

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