5dyl

Structural highlights

Function

KGP_PLAVS Serine/threonine protein kinase which acts as a downstream effector of the second messenger cGMP. Controls the release of Ca(2+) from intracellular stores by regulating phosphoinositide biosynthesis. Ca(2+) signals are essential for merozoite and sporozoite invasion and egress from host hepatocytes and erythrocytes, and, in the mosquito vector, for gametocyte activation, and ookinete and sporozoite motility (By similarity). During the host liver stage, regulates the initial invasion of host hepatocytes by sporozoites by regulating sporozoite motility and microneme exocytosis. Following parasite development in the hepatocytes, required for the release of merosomes, a vesicle containing the mature merozoites (By similarity). During the asexual blood stage, required for the progression from schizont to the ring stage following merozoite invasion of host erythrocytes and for merozoite egress. Regulates merozoite egress by promoting the release of exonemes and micronemes which contain proteins essential for egress. Phosphorylates CDPK1 predominantly at the late schizont stage; phosphorylation at 'Ser-64' regulates CDPK1 protein-protein interaction and phosphorylation at 'Thr-231' may regulate CDPK1 kinase activity. In the mosquito vector, required for the initiation of gametogenesis induced by xanthurenic acid, specifically the gametocyte differentiation from the crescent-shaped form to the spherical form (By similarity). Required for the gliding motility of ookinetes to reach and penetrate the midgut epithelium by promoting Ca(2+)-mediated activation of CDPK1 and CDPK4. Also required for microneme secretion in ookinete by promoting Ca(2+)-mediated activation of CDPK3 (By similarity).[UniProtKB:A0A509AKL0][UniProtKB:Q8I719]

References

1. ↑ El Bakkouri M, Kouidmi I, Wernimont AK, Amani M, Hutchinson A, Loppnau P, Kim JJ, Flueck C, Walker JR, Seitova A, Senisterra G, Kakihara Y, Kim C, Blackman MJ, Calmettes C, Baker DA, Hui R. Structures of the cGMP-dependent protein kinase in malaria parasites reveal a unique structural relay mechanism for activation. Proc Natl Acad Sci U S A. 2019 Jul 9;116(28):14164-14173. doi:, 10.1073/pnas.1905558116. Epub 2019 Jun 25. PMID:31239348 doi:http://dx.doi.org/10.1073/pnas.1905558116