Structure and dynamics of apical membrane antigen 1 from Plasmodium falciparum FVO.
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| Abstract |
Apical membrane antigen 1 (AMA1) interacts with RON2 to form a protein complex that plays a key role in the invasion of host cells by malaria parasites. Blocking this protein-protein interaction represents a potential route to controlling malaria and related parasitic diseases, but the polymorphic nature of AMA1 has proven to be a major challenge to vaccine-induced antibodies and peptide inhibitors exerting strain-transcending inhibitory effects. Here we present the X-ray crystal structure of AMA1 domains I and II from Plasmodium falciparum strain FVO. We compare our new structure to those of AMA1 from P. falciparum 3D7 and Plasmodium vivax. A combination of normalized B factor analysis and computational methods has been used to investigate the flexibility of the domain I loops and how this correlates with their roles in determining the strain specificity of human antibody responses and inhibitory peptides. We also investigated the domain II loop, a key region involved in inhibitor binding, by comparison of multiple AMA1 crystal structures. Collectively, these results provide valuable insights that should contribute to the design of strain-transcending agents targeting P. falciparum AMA1.
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| Authors | San Sui Lim, Wei Yang, Bankala Krishnarjuna, Komagal Kannan Sivaraman, Indu R Chandrashekaran, Itamar Kass, Christopher A MacRaild, Shane M Devine, Cael O Debono, Robin F Anders, Martin J Scanlon, Peter J Scammells, Raymond S Norton, Sheena McGowan |
| Journal | Biochemistry (Biochemistry) Vol. 53 Issue 46 Pg. 7310-20 (Nov 25 2014) ISSN: 1520-4995 [Electronic] United States |
| PMID | 25360546 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
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