Dataset Information

Crystallization and X-ray analysis of the Schistosoma mansoni guanidino kinase.

ABSTRACT: The 716-amino-acid guanidino kinase from the parasitic flatworm Schistosoma mansoni results from the fusion of two guanidino kinase subunits. Crystals of this 80 kDa protein have been obtained in the monoclinic space group P2(1), with unit-cell parameters a = 52.7, b = 122.1, c = 63.2 A, beta = 108.5 degrees . Synchrotron data were collected to 2.8 A resolution on ESRF beamline ID29. The structure was solved by the molecular-replacement method, using the 357-amino-acid structure of the arginine kinase from Trypanosoma cruzi as the search model.

SUBMITTER: Awama AM

PROVIDER: S-EPMC2531260 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Publications

Crystallization and X-ray analysis of the Schistosoma mansoni guanidino kinase.

Awama Ayman M AM Paracuellos Patricia P Laurent Sabine S Dissous Colette C Marcillat Olivier O Gouet Patrice P

Acta crystallographica. Section F, Structural biology and crystallization communications 20080820 Pt 9

The 716-amino-acid guanidino kinase from the parasitic flatworm Schistosoma mansoni results from the fusion of two guanidino kinase subunits. Crystals of this 80 kDa protein have been obtained in the monoclinic space group P2(1), with unit-cell parameters a = 52.7, b = 122.1, c = 63.2 A, beta = 108.5 degrees . Synchrotron data were collected to 2.8 A resolution on ESRF beamline ID29. The structure was solved by the molecular-replacement method, using the 357-amino-acid structure of the arginine ...[more]

PMID: 18765922

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Project description:The Venus kinase receptor (VKR) is a single transmembrane molecule composed of an intracellular tyrosine kinase domain close to that of insulin receptor and an extracellular Venus Flytrap (VFT) structure similar to the ligand binding domain of many class C G protein coupled receptors. This receptor tyrosine kinase (RTK) was first discovered in the platyhelminth parasite Schistosoma mansoni, then in a large variety of invertebrates. A single vkr gene is found in most genomes, except in S. mansoni in which two genes Smvkr1 and Smvkr2 exist. VKRs form a unique family of RTKs present only in invertebrates and their biological functions are still to be discovered. In this work, we show that SmVKRs are expressed in the reproductive organs of S. mansoni, particularly in the ovaries of female worms. By transcriptional analyses evidence was obtained that both SmVKRs fulfill different roles during oocyte maturation. Suppression of Smvkr expression by RNA interference induced spectacular morphological changes in female worms with a strong disorganization of the ovary, which was dominated by the presence of primary oocytes, and a defect of egg formation. Following expression in Xenopus oocytes, SmVKR1 and SmVKR2 receptors were shown to be activated by distinct ligands which are L-Arginine and calcium ions, respectively. Signalling analysis in Xenopus oocytes revealed the capacity of SmVKRs to activate the PI3K/Akt/p70S6K and Erk MAPK pathways involved in cellular growth and proliferation. Additionally, SmVKR1 induced phosphorylation of JNK (c-Jun N-terminal kinase). Activation of JNK by SmVKR1 was supported by the results of yeast two-hybrid experiments identifying several components of the JNK pathway as specific interacting partners of SmVKR1. In conclusion, these results demonstrate the functions of SmVKR in gametogenesis, and particularly in oogenesis and egg formation. By eliciting signalling pathways potentially involved in oocyte proliferation, growth and migration, these receptors control parasite reproduction and can therefore be considered as potential targets for anti-schistosome therapies.

Dataset Information

Crystallization and X-ray analysis of the Schistosoma mansoni guanidino kinase.

Publications

Crystallization and X-ray analysis of the Schistosoma mansoni guanidino kinase.

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