Structure of a gametocyte protein essential for sexual development in Plasmodium falciparum.
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.
Sharma
Amit
A
Malaria group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India. asharma@icgeb.res.in
Sharma
Indu
I
Kogkasuriyachai
Darin
D
Kumar
Nirbhay
N
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D019281:Dimerization; D005718:Gametogenesis / Q000502:physiology; D019077:Helix-Turn-Helix Motifs; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000737:chemistry* / Q000254:growth & development; D011392:Proline; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000737:chemistry* / Q000378:metabolism*; D016053:RNA, Protozoan / Q000378:metabolism; D012098:Reproduction / Q000502:physiology; D018909:src Homology Domains
D000953:Antigens, Protozoan; D015800:Protozoan Proteins; D016053:RNA, Protozoan; C069962:Pfg25-27 protein, Plasmodium falciparum; D011392:Proline