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Malarial EBA-175 region VI crystallographic structure reveals a KIX-like binding interface.
- Source :
-
Journal of molecular biology [J Mol Biol] 2008 Jan 18; Vol. 375 (3), pp. 773-81. Date of Electronic Publication: 2007 Nov 01. - Publication Year :
- 2008
-
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.
- Subjects :
- Amino Acid Sequence
Animals
Binding Sites
Crystallography, X-Ray
Cysteine chemistry
Dimerization
Disulfides chemistry
Duffy Blood-Group System chemistry
Humans
Hydrogen-Ion Concentration
Hydrophobic and Hydrophilic Interactions
Models, Molecular
Molecular Sequence Data
Molecular Weight
Plasmodium falciparum pathogenicity
Protein Binding
Protein Folding
Protein Structure, Secondary
Protein Structure, Tertiary
Sequence Homology, Amino Acid
Water chemistry
Antigens, Protozoan
Duffy Blood-Group System metabolism
Erythrocytes metabolism
Malaria blood
Plasmodium falciparum chemistry
Plasmodium falciparum metabolism
Protozoan Proteins blood
Subjects
Details
- Language :
- English
- ISSN :
- 1089-8638
- Volume :
- 375
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 18036613
- Full Text :
- https://doi.org/10.1016/j.jmb.2007.10.071