Crystal Structure of Calcium Binding Protein-5 from Entamoeba histolytica and Its Involvement in Initiation of Phagocytosis of Human Erythrocytes

Sanjeev Kumar , Saima Aslam , Mohit Mazumder, Pradeep Dahiya, Aruna Murmu, Babu A. Manjasetty, Rana Zaidi

PLoS Pathog (2014)10(12): e1004532

Speaker: Jia-Yien Woo (武珈言)                                  Time: 13:10~14:00, June. 17, 2015

Commentator: Dr. Shu-Ying Wang (王淑鶯 老師)     Place: Room 601

Abstract:

        Entamoeba histolytica is an anaerobic parasitic protozoan with an estimated 50 million people infected each year, particularly in developing countries causing a high level of morbidity and mortality.¹ Phagocytosis is the major route of food intake by this parasite and is responsible for its virulence. The genome of this organism encodes 27 EF-hand containing calcium binding proteins suggesting an intricate Ca²⁺ signaling system that plays crucial role in phagocytosis and pathogenesis.² Calcium Binding Protein-5 from E. histolytica (EhCaBP5) is one of these CaBPs that displays sequence similarity with Calmodulin (CaM). Its expression is very sensitive to serum starvation and it seems to be involved in binding to myosin I. Interestingly, the crystal structure of EhCaBP5 showed more structural similarity with essential light chain (ELC) of myosin than the typical CaM. The results of Surface plasmon resonance (SPR) suggest that EhCaBP5 could be a light chain of myosin and interacts with IQ motif of Myosin IB. This specific interaction was confirmed by the observation of the co-localization of EhCaBP5 and myosin 1B in phagocytic cups, and the down regulating EhCaBP5 carried out to show that EhCaBP5 indeed binds myosin IB in Ca²⁺ independent manner. The authors also had taken red blood cells uptake assay to show that EhCaBP5-IQ motif complex participates in erythrophagocytosis. The authors conclude that phagocytosis in E. histolytica is regulated by a number of CaBPs including EhCaBP5 that regulates cytoskeletal dynamics and phagocytic cup formation with the help of myosin 1B.

References:

1.         Stanley SL, Jr. (2003) Amoebiasis. Lancet 361: 1025–1034.

2.         Alok Bhattacharya,Narendra Padhan,Ruchi Jain,and Sudha Bhattacharya (2006) Calcium-Binding Proteins of Entamoeba histolytica. Archives of Medical Research(37):221–225