Malarial EBA-175 region VI crystallographic structure reveals a KIX-like binding interface.


Withers-Martinez, C; Haire, LF; Hackett, F; Walker, PA; Howell, SA; Smerdon, SJ; Dodson, GG; Blackman, MJ; (2008) Malarial EBA-175 region VI crystallographic structure reveals a KIX-like binding interface. Journal of molecular biology, 375 (3). pp. 773-81. ISSN 0022-2836 DOI: https://doi.org/10.1016/j.jmb.2007.10.071

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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.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
PubMed ID: 18036613
Web of Science ID: 253124600016
URI: http://researchonline.lshtm.ac.uk/id/eprint/1544224

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