tailieunhanh - Báo cáo khoa học: FH8 – a small EF-hand protein from Fasciola hepatica

Vaccine and drug development for fasciolasis rely on a thorough under-standing of the mechanisms involved in parasite–host interactions. FH8 is an 8 kDa protein secreted by the parasite Fasciola hepaticain the early stages of infection. | 1FEBS Journal FH8 - a small EF-hand protein from Fasciola hepatica Hugo Fraga1 Tiago Q. Faria2 Filipe Pinto1 Agostinho Almeida3 Rui M. M. Brito2 4 and Ana M. Damas1 5 1 IBMC Institute for Molecular and CellBiology University of Porto Portugal 2 Center for Neuroscience and CellBiology University of Coimbra Portugal 3 REQUIMTE Faculdade de Farmacia Departamento de Quimica-Fisica University of Porto Portugal 4 Chemistry Department Faculty of Science and Technology University of Coimbra Portugal 5 ICBAS Instituto de Ciencias Biomedicas de AbelSalazar University of Porto Portugal Keywords calcium binding protein fasciolasis FH8 Fasciola hepatica sensor protein Correspondence A. M. Damas IBMC Institute for Molecular and CellBiology University of Porto R. Campo Alegre 823 4150-180 Porto Portugal Fax 351 226099157 Tel 351 226074900 E-mail amdamas@ Received 15 July 2010 revised 24 September 2010 accepted 11 October 2010 doi Vaccine and drug development for fasciolasis rely on a thorough understanding of the mechanisms involved in parasite-host interactions. FH8 is an 8 kDa protein secreted by the parasite Fasciola hepatica in the early stages of infection. Sequence analysis revealed that FH8 has two EF-hand Ca2 -binding motifs and our experimental data show that the protein binds Ca2 and that this induces conformational alterations thus causing it to behave like a sensor protein. Moreover FH8 displays low affinity for Ca2 Kobs 104 M 1 and is highly stable in its apo and Ca2 -loaded states. Homology models were built for FH8 in both states. It has only one globular domain with two binding sites and appropriate groups in the positions for coordination of the metal ions. However an unusually high content of positively charged amino acids in one of the binding sites when compared with the prototypical sensor proteins potentially affects the protein s affinity for Ca2 . The only Cys present in FH8 conserved in the homologous proteins of

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