title: Crystal structure of the C-terminal domain of tubulin-binding cofactor C from Leishmania major.
abstract: Tubulin-binding cofactor C stimulates GTPase activity and contributes to the release of the heterodimeric α/β-tubulin from a super-complex of tubulin monomers and two ancillary cofactors. We have determined the 2.2 Å resolution crystal structure of the C-terminal domain of tubulin-binding cofactor C from Leishmania major based on single wavelength anomalous dispersion measurements targeting a selenomethionine derivative. Although previously predicted to consist of two domains the structure is best described as a single domain dominated by a right-handed β-helix of five turns that form a triangular prism. One face of the prism is covered by the C-terminal residues leaving another face solvent exposed. Comparisons with an orthologous human GTPase activating protein match key residues involved in binding nucleotide and identify the face of the β-helix fold likely involved in interacting with the β-tubulin:GTP complex.
authors.affiliation: Division of Biological Chemistry & Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
authors.forename: Keri L
authors.initials: KL
authors.lastname: Barrack
authors.affiliation: Division of Biological Chemistry & Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
authors.forename: Paul K
authors.initials: PK
authors.lastname: Fyfe
authors.affiliation: Division of Biological Chemistry & Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Finney
authors.affiliation: Division of Biological Chemistry & Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK. Electronic address: w.n.hunter@dundee.ac.uk.
authors.forename: William N
authors.initials: WN
authors.lastname: Hunter
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D018320:Leishmania major / Q000737:chemistry*; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017385:Sequence Homology
chemical_list: D018832:Molecular Chaperones; C455270:tubulin-specific chaperone C
keywords: CARP domain; Crystal structure; Tubulin-binding protein; β-helix