TY - JOUR
T1 - Structure of a gametocyte protein essential for sexual development in Plasmodium falciparum
AU - Sharma, Amit
AU - Sharma, Indu
AU - Kogkasuriyachai, Darin
AU - Kumar, Nirbhay
N1 - Funding Information:
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.
PY - 2003/3/1
Y1 - 2003/3/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/0037336247
UR - https://www.scopus.com/pages/publications/0037336247#tab=citedBy
U2 - 10.1038/nsb899
DO - 10.1038/nsb899
M3 - Article
C2 - 12577051
AN - SCOPUS:0037336247
SN - 1072-8368
VL - 10
SP - 197
EP - 203
JO - Nature Structural Biology
JF - Nature Structural Biology
IS - 3
ER -