Plasmodium Myosin A Drives Parasite Invasion by an Atypical Force Generating Mechanism

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Jul 25

PMID 31337750

Citations 28

Authors

Julien Robert-Paganin

James P Robblee

Daniel Auguin

Thomas C A Blake

Carol S Bookwalter

Elena B Krementsova

Dihia Moussaoui

Michael J Previs

Guillaume Jousset

Jake Baum

Kathleen M Trybus

Anne Houdusse

Affiliations

Soon will be listed here.

Abstract

Plasmodium parasites are obligate intracellular protozoa and causative agents of malaria, responsible for half a million deaths each year. The lifecycle progression of the parasite is reliant on cell motility, a process driven by myosin A, an unconventional single-headed class XIV molecular motor. Here we demonstrate that myosin A from Plasmodium falciparum (PfMyoA) is critical for red blood cell invasion. Further, using a combination of X-ray crystallography, kinetics, and in vitro motility assays, we elucidate the non-canonical interactions that drive this motor's function. We show that PfMyoA motor properties are tuned by heavy chain phosphorylation (Ser19), with unphosphorylated PfMyoA exhibiting enhanced ensemble force generation at the expense of speed. Regulated phosphorylation may therefore optimize PfMyoA for enhanced force generation during parasite invasion or for fast motility during dissemination. The three PfMyoA crystallographic structures presented here provide a blueprint for discovery of specific inhibitors designed to prevent parasite infection.

Citing Articles

High-resolution structures of Myosin-IC reveal a unique actin-binding orientation, ADP release pathway, and power stroke trajectory.

Chavali S, Carman P, Shuman H, Ostap E, Sindelar C Proc Natl Acad Sci U S A. 2025; 122(9):e2415457122.

PMID: 40014570 PMC: 11892617. DOI: 10.1073/pnas.2415457122.

High resolution structures of Myosin-IC reveal a unique actin-binding orientation, ADP release pathway, and power stroke trajectory.

Chavali S, Carman P, Shuman H, Ostap E, Sindelar C bioRxiv. 2025; .

PMID: 39829824 PMC: 11741418. DOI: 10.1101/2025.01.10.632429.

Motor domain phosphorylation increases nucleotide exchange and turns MYO6 into a faster and stronger motor.

de Jonge J, Graw A, Kargas V, Batters C, Montanarella A, OLoughlin T Nat Commun. 2024; 15(1):6716.

PMID: 39112473 PMC: 11306250. DOI: 10.1038/s41467-024-49898-3.

Omecamtiv mecarbil and Mavacamten target the same myosin pocket despite opposite effects in heart contraction.

Auguin D, Robert-Paganin J, Rety S, Kikuti C, David A, Theumer G Nat Commun. 2024; 15(1):4885.

PMID: 38849353 PMC: 11161628. DOI: 10.1038/s41467-024-47587-9.

Omecamtiv mecarbil and Mavacamten target the same myosin pocket despite antagonistic effects in heart contraction.

Auguin D, Robert-Paganin J, Rety S, Kikuti C, David A, Theumer G bioRxiv. 2023; .

PMID: 38014327 PMC: 10680719. DOI: 10.1101/2023.11.15.567213.

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