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, Wim G J Hol

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)77-88
Number of pages12
JournalJournal of Molecular Biology
Volume372
Issue number1
DOIs
StatePublished - Sep 7 2007
Externally publishedYes

Fingerprint

Nonmuscle Myosin Type IIA
Malaria
Tail
Parasites
Proteins
Actomyosin

Keywords

  • apicomplexa
  • gliding motility
  • IQ motif
  • myosin light chain

ASJC Scopus subject areas

  • Virology

Cite this

Bosch, J., Turley, S., Roach, C. M., Daly, T. M., Bergman, L. W., & Hol, W. G. J. (2007). The Closed MTIP-Myosin A-Tail Complex from the Malaria Parasite Invasion Machinery. Journal of Molecular Biology, 372(1), 77-88. https://doi.org/10.1016/j.jmb.2007.06.016

The Closed MTIP-Myosin A-Tail Complex from the Malaria Parasite Invasion Machinery. / Bosch, Jürgen; Turley, Stewart; Roach, Claudia M.; Daly, Thomas M.; Bergman, Lawrence W.; Hol, Wim G J.

In: Journal of Molecular Biology, Vol. 372, No. 1, 07.09.2007, p. 77-88.

Research output: Contribution to journalArticle

Bosch, J, Turley, S, Roach, CM, Daly, TM, Bergman, LW & Hol, WGJ 2007, 'The Closed MTIP-Myosin A-Tail Complex from the Malaria Parasite Invasion Machinery', Journal of Molecular Biology, vol. 372, no. 1, pp. 77-88. https://doi.org/10.1016/j.jmb.2007.06.016
Bosch, Jürgen ; Turley, Stewart ; Roach, Claudia M. ; Daly, Thomas M. ; Bergman, Lawrence W. ; Hol, Wim G J. / The Closed MTIP-Myosin A-Tail Complex from the Malaria Parasite Invasion Machinery. In: Journal of Molecular Biology. 2007 ; Vol. 372, No. 1. pp. 77-88.
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