Paper Citing NAMD - Abstract
Lim, San Sui; Yang, Wei; Krishnarjuna, Bankala; Sivaraman, Komagal Kannan; Chandrashekaran, Indu R.; Kass, Itamar; MacRaild, Christopher A.; Devine, Shane M.; Debono, Cael O.; Anders, Robin F.; Scanlon, Martin J.; Scammells, Peter J.; Norton, Raymond S.; McGowan, Sheena
Structure and Dynamics of Apical Membrane Antigen 1 from Plasmodium falciparum FVO
BIOCHEMISTRY, 53:7310-7320, NOV 25 2014
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 proteinprotein 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.
