Structure and Dynamics of Apical Membrane Antigen 1 from Plasmodium falciparum FVO Academic Article uri icon

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.

authors

  • Lim, San Sui
  • Yang, Wei
  • Krishnarjuna, Bankala
  • Kannan Sivaraman, Komagal
  • 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

publication date

  • November 25, 2014