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The Closed MTIP-Myosin A-Tail Complex from the Malaria Parasite Invasion Machinery
Journal article   Open access   Peer reviewed

The Closed MTIP-Myosin A-Tail Complex from the Malaria Parasite Invasion Machinery

Jürgen Bosch, Stewart Turley, Claudia M Roach, Thomas M Daly, Lawrence W Bergman and Wim G.J Hol
Journal of molecular biology, v 372(1), pp 77-88
2007
PMID: 17628590
url
https://doi.org/10.1016/j.jmb.2007.06.016View
Published, Version of Record (VoR) Open

Abstract

IQ motif myosin light chain apicomplexa gliding motility
The Myosin A-tail interacting protein (MTIP) of the malaria parasite links the actomyosin motor of the host cell invasion machinery to its inner membrane complex. We report here that at neutral pH Plasmodium falciparum MTIP in complex with Myosin A adopts a compact conformation, with its two domains completely surrounding the Myosin A-tail helix, dramatically different from previously observed extended MTIP structures. Crystallographic and mutagenesis studies show that H810 and K813 of Myosin A are key players in the formation of the compact MTIP:Myosin A complex. Only the unprotonated state of Myosin A-H810 is compatible with the compact complex. Most surprisingly, every side-chain atom of Myosin A-K813 is engaged in contacts with MTIP. While this side-chain was previously considered to prevent a compact conformation of MTIP with Myosin A, it actually appears to be essential for the formation of the compact complex. The hydrophobic pockets and adaptability seen in the available series of MTIP structures bodes well for the discovery of inhibitors of cell invasion by malaria parasites.

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
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