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Title: Towards a molecular understanding of the apicomplexan actin motor: on a road to novel targets for malaria remedies?

Abstract

In this review, current structural understanding of the apicomplexan glideosome and actin regulation is described. Apicomplexan parasites are the causative agents of notorious human and animal diseases that give rise to considerable human suffering and economic losses worldwide. The most prominent parasites of this phylum are the malaria-causing Plasmodium species, which are widespread in tropical and subtropical regions, and Toxoplasma gondii, which infects one third of the world’s population. These parasites share a common form of gliding motility which relies on an actin–myosin motor. The components of this motor and the actin-regulatory proteins in Apicomplexa have unique features compared with all other eukaryotes. This, together with the crucial roles of these proteins, makes them attractive targets for structure-based drug design. In recent years, several structures of glideosome components, in particular of actins and actin regulators from apicomplexan parasites, have been determined, which will hopefully soon allow the creation of a complete molecular picture of the parasite actin–myosin motor and its regulatory machinery. Here, current knowledge of the function of this motor is reviewed from a structural perspective.

Authors:
 [1];  [2];  [2];  [1];  [2];  [2];  [3]
+ Show Author Affiliations
  1. University of Oulu, PO Box 3000, 90014 Oulu (Finland)
  2. (Germany)
  3. (Norway)
Publication Date:
OSTI Identifier:
22375718
Resource Type:
Journal Article
Resource Relation:
Journal Name: Acta crystallographica. Section F, Structural biology communications; Journal Volume: 71; Journal Issue: Pt 5; Other Information: PMCID: PMC4427158; PMID: 25945702; PUBLISHER-ID: hv5284; PUBLISHER-ID: S2053230X1500391X; OAI: oai:pubmedcentral.nih.gov:4427158; Copyright (c) Kumpula & Kursula 2015; This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY; CURRENTS; DESIGN; LOSSES; MICROTUBULES; PLASMA; REVIEWS

Citation Formats

Kumpula, Esa-Pekka, Helmholtz Centre for Infection Research, Notkestrasse 85, 22607 Hamburg, German Electron Synchrotron, Notkestrasse 85, 22607 Hamburg, Kursula, Inari, E-mail: inari.kursula@helmholtz-hzi.de, Helmholtz Centre for Infection Research, Notkestrasse 85, 22607 Hamburg, German Electron Synchrotron, Notkestrasse 85, 22607 Hamburg, and University of Bergen, Jonas Lies vei 91, 5009 Bergen. Towards a molecular understanding of the apicomplexan actin motor: on a road to novel targets for malaria remedies?. United States: N. p., 2015. Web. doi:10.1107/S2053230X1500391X.
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Kumpula, Esa-Pekka, Helmholtz Centre for Infection Research, Notkestrasse 85, 22607 Hamburg, German Electron Synchrotron, Notkestrasse 85, 22607 Hamburg, Kursula, Inari, E-mail: inari.kursula@helmholtz-hzi.de, Helmholtz Centre for Infection Research, Notkestrasse 85, 22607 Hamburg, German Electron Synchrotron, Notkestrasse 85, 22607 Hamburg, & University of Bergen, Jonas Lies vei 91, 5009 Bergen. Towards a molecular understanding of the apicomplexan actin motor: on a road to novel targets for malaria remedies?. United States. doi:10.1107/S2053230X1500391X.
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Kumpula, Esa-Pekka, Helmholtz Centre for Infection Research, Notkestrasse 85, 22607 Hamburg, German Electron Synchrotron, Notkestrasse 85, 22607 Hamburg, Kursula, Inari, E-mail: inari.kursula@helmholtz-hzi.de, Helmholtz Centre for Infection Research, Notkestrasse 85, 22607 Hamburg, German Electron Synchrotron, Notkestrasse 85, 22607 Hamburg, and University of Bergen, Jonas Lies vei 91, 5009 Bergen. Thu . "Towards a molecular understanding of the apicomplexan actin motor: on a road to novel targets for malaria remedies?". United States. doi:10.1107/S2053230X1500391X.
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@article{osti_22375718,
title = {Towards a molecular understanding of the apicomplexan actin motor: on a road to novel targets for malaria remedies?},
author = {Kumpula, Esa-Pekka and Helmholtz Centre for Infection Research, Notkestrasse 85, 22607 Hamburg and German Electron Synchrotron, Notkestrasse 85, 22607 Hamburg and Kursula, Inari, E-mail: inari.kursula@helmholtz-hzi.de and Helmholtz Centre for Infection Research, Notkestrasse 85, 22607 Hamburg and German Electron Synchrotron, Notkestrasse 85, 22607 Hamburg and University of Bergen, Jonas Lies vei 91, 5009 Bergen},
abstractNote = {In this review, current structural understanding of the apicomplexan glideosome and actin regulation is described. Apicomplexan parasites are the causative agents of notorious human and animal diseases that give rise to considerable human suffering and economic losses worldwide. The most prominent parasites of this phylum are the malaria-causing Plasmodium species, which are widespread in tropical and subtropical regions, and Toxoplasma gondii, which infects one third of the world’s population. These parasites share a common form of gliding motility which relies on an actin–myosin motor. The components of this motor and the actin-regulatory proteins in Apicomplexa have unique features compared with all other eukaryotes. This, together with the crucial roles of these proteins, makes them attractive targets for structure-based drug design. In recent years, several structures of glideosome components, in particular of actins and actin regulators from apicomplexan parasites, have been determined, which will hopefully soon allow the creation of a complete molecular picture of the parasite actin–myosin motor and its regulatory machinery. Here, current knowledge of the function of this motor is reviewed from a structural perspective.},
doi = {10.1107/S2053230X1500391X},
journal = {Acta crystallographica. Section F, Structural biology communications},
number = Pt 5,
volume = 71,
place = {United States},
year = {Thu Apr 16 00:00:00 EDT 2015},
month = {Thu Apr 16 00:00:00 EDT 2015}
}
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Journal Article:
DOI:  10.1107/S2053230X1500391X
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