4R1A

Crystal Structure of FVO strain Plasmodium falciparum AMA1

Summary for 4R1A

• Entry DOI: 10.2210/pdb4r1a/pdb
• Related: 4R19 4R1B 4R1C
• Descriptor: Apical membrane antigen 1 (2 entities in total)
• Functional Keywords: pan fold, erythrocyte invasion by merozoites, ron2, moving junction complex, cell invasion
• Biological source: Plasmodium falciparum FCR-3/Gambia
• Cellular location: Membrane; Single-pass type I membrane protein: P50490
• Total number of polymer chains: 1
• Total formula weight: 38333.81

Authors

Lim, S.S.,Norton, R.S.,McGowan, S. (deposition date: 2014-08-04, release date: 2015-01-14, Last modification date: 2024-11-20)

Primary citation

Lim, S.S.,Yang, W.,Krishnarjuna, B.,Kannan Sivaraman, K.,Chandrashekaran, I.R.,Kass, I.,MacRaild, C.A.,Devine, S.M.,Debono, C.O.,Anders, R.F.,Scanlon, M.J.,Scammells, P.J.,Norton, R.S.,McGowan, S.
Structure and Dynamics of Apical Membrane Antigen 1 from Plasmodium falciparum FVO.
Biochemistry, 53:7310-7320, 2014

PubMed 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.

PubMed: 25360546
DOI: 10.1021/bi5012089

Experimental method

X-RAY DIFFRACTION (2 Å)