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Structure of a gametocyte protein essential for sexual development in Plasmodium falciparum

Nature Structural & Molecular Biology volume 10, pages 197–203 (2003)Cite this article

Abstract

Malaria transmission is dependent on the development of sexual forms of Plasmodium falciparum, called gametocytes, in the vertebrate host. Pfg27 is an abundantly expressed sexual stage–specific protein that is essential for gametocytogenesis in P. falciparum. We describe the crystal structure of Pfg27, which reveals a novel fold composed of two pseudo dyad–related repeats of the helix-turn-helix motif. Structurally equivalent helices of each repeat either form a dimer interface or interact with RNA in vitro. One side of the dimer presents an unprecedented juxtaposition of four polyproline (PXXP) motifs. Preliminary binding data indicate that these sites are capable of binding Src homology-3 (SH3) modules. Molecular modeling suggests that the dimer can accommodate two SH3 modules simultaneously, potentially enabling molecular crosstalk between SH3-containing proteins. The structural and initial biochemical evidence suggests that Pfg27 may serve as a platform for RNA and SH3 binding.

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Figure 1: Overall structure of Pfg27.
Figure 2: The dimeric form of Pfg27.
Figure 3: Interaction of Pfg27 with RNA.
Figure 4: Interaction of Pfg27 with SH3 modules.

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Acknowledgements

We are grateful to D. Stuart (Oxford) for his encouragement throughout this project. We thank the Medical Research Council, UK and the staff of BM14 (ESRF, Grenoble, France) for facilitating data collection. We thank S. Jameel (ICGEB) for providing the GST constructs. We also thank past and present members of ICGEB, C. Chitnis, S. Garman and S. Krishnaswamy for help and suggestions. D.K. provided the clone for overexpression of Pfg27. N.K. is supported by a grant from the National Institutes of Health, and A.S. is funded by an International Wellcome Trust Senior Research Fellowship.

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Authors and Affiliations

  1. Malaria group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India

    Amit Sharma & Indu Sharma

  2. Department of Molecular Microbiology and Immunology, Hopkins Malaria Research Institute, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, 21205, Maryland, USA

    Darin Kogkasuriyachai & Nirbhay Kumar

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Correspondence to Amit Sharma.

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Sharma, A., Sharma, I., Kogkasuriyachai, D. et al. Structure of a gametocyte protein essential for sexual development in Plasmodium falciparum. Nat Struct Mol Biol 10, 197–203 (2003). https://doi.org/10.1038/nsb899

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