Vital functions of the malarial ookinete protein CTRP reside in the A domains

Chandra Ramakrishnan; Johannes T. Dessens; Rebecca Armson; Sofia B. Pinto; Arthur M. Talman; Andrew M. Blagborough; Robert E. Sinden

doi:10.1016/j.ijpara.2011.05.007

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Vital functions of the malarial ookinete protein CTRP reside in the A domains

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Vital functions of the malarial ookinete protein CTRP reside in the A domains

Chandra Ramakrishnan, Johannes T. Dessens, Rebecca Armson, Sofia B. Pinto, Arthur M. Talman, Andrew M. Blagborough et Robert E. Sinden

International journal for parasitology, Vol.41(10), pp.1029-1039

15/08/2011

DOI: https://doi.org/10.1016/j.ijpara.2011.05.007

PMID: 21729699

Résumé

The transformation of malaria ookinetes into oocysts occurs in the mosquito midgut and is a major bottleneck for parasite transmission. The secreted ookinete surface protein CTRP (circumsporozoite- and TRAP-related protein) is essential for this transition, and hence constitutes a potential target for malaria transmission blockade. CTRP is a modular multidomain protein containing six tandem von Willebrand factor A-like (A) domains and seven tandem thrombospondin-like (TS) domains. Here, we present the first structure-function analysis of CTRP using genetically modified Plasmodium berghei parasites expressing mutant versions of the ctrp gene. Our data show that the A domains of CTRP are critical for ookinete gliding motility and oocyst formation whilst unexpectedly, its TS domains are fully redundant. These results may have important implications for the design of CTRP-based transmission blocking strategies.

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Titre: Vital functions of the malarial ookinete protein CTRP reside in the A domains
Créateurs - sans rôle: Chandra Ramakrishnan - Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College London, South Kensington Campus, London SW7 2AZ, UK Department of Pathogen Molecular Biology, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK Department of Zoology, University of Oxford, The Tinbergen Building, South Parks Road, Oxford OX1 3PS, UK
Johannes T. Dessens - Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College London, South Kensington Campus, London SW7 2AZ, UK Department of Pathogen Molecular Biology, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK Department of Zoology, University of Oxford, The Tinbergen Building, South Parks Road, Oxford OX1 3PS, UK
Rebecca Armson - Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College London, South Kensington Campus, London SW7 2AZ, UK Department of Pathogen Molecular Biology, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK Department of Zoology, University of Oxford, The Tinbergen Building, South Parks Road, Oxford OX1 3PS, UK
Sofia B. Pinto - Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College London, South Kensington Campus, London SW7 2AZ, UK Department of Pathogen Molecular Biology, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK Department of Zoology, University of Oxford, The Tinbergen Building, South Parks Road, Oxford OX1 3PS, UK
Arthur M. Talman - Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College London, South Kensington Campus, London SW7 2AZ, UK Department of Pathogen Molecular Biology, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK Department of Zoology, University of Oxford, The Tinbergen Building, South Parks Road, Oxford OX1 3PS, UK
Andrew M. Blagborough - University of Oxford
Robert E. Sinden - Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College London, South Kensington Campus, London SW7 2AZ, UK Department of Pathogen Molecular Biology, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK Department of Zoology, University of Oxford, The Tinbergen Building, South Parks Road, Oxford OX1 3PS, UK
Détails de publication: International journal for parasitology, Vol.41(10), pp.1029-1039
Nombre de pages: 11
Identifiants: 99159088309311
Unité académique: Maladies Infectieuses et Vecteurs : Ecologie, Génétique, Evolution et Contrôle - MIVEGEC
Langue: English
Type de ressource: Journal article