Download MendeleyMalarial EBA-175 Region VI Crystallographic Structure Reveals a KIX-Like Binding Interface
Withers-Martinez, C., Haire, L.F., Hackett, F., Walker, P.A., Howell, S.A., Smerdon, S.J., Dodson, G.G., Blackman, M.J.(2008) J Mol Biol 375: 773-781
- PubMed: 18036613
- DOI: https://doi.org/10.1016/j.jmb.2007.10.071
- Primary Citation of Related Structures:
2RJI - PubMed Abstract:
The malaria parasite proliferates in the bloodstream of its vertebrate host by invading and replicating within erythrocytes. To achieve successful invasion, a number of discrete and essential events need to take place at the parasite-host cell interface. Erythrocyte-binding antigen 175 (EBA-175) is a member of a family of Plasmodium falciparum erythrocyte-binding proteins involved in the formation of a tight junction, a necessary step in invasion. Here we present the crystal structure of EBA-175 region VI (rVI), a cysteine-rich domain that is highly conserved within the protein family and is essential for EBA-175 trafficking. The structure was solved by selenomethionine single-wavelength anomalous dispersion at 1.8 A resolution. It reveals a homodimer, containing in each subunit a compact five-alpha-helix core that is stabilized by four conserved disulfide bridges. rVI adopts a novel fold that is likely conserved across the protein family, indicating a conserved function. It shows no similarity to the Duffy-binding-like domains of EBA-175 involved in erythrocyte binding, indicating a distinct role. Remarkably, rVI possesses structural features related to the KIX-binding domain of the coactivator CREB-binding protein, supporting the binding and trafficking roles that have been ascribed to it and providing a rational basis for further experimental investigation of its function.
Organizational Affiliation:
Division of Parasitology, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK. cmartin@nimr.mrc.ac.uk
