title: The centriolar protein CPAP G-box: an amyloid fibril in a single domain.
abstract: Centrioles are evolutionarily conserved cylindrical cell organelles with characteristic radial symmetry. Despite their considerable size (400 nm × 200 nm, in humans), genetic studies suggest that relatively few protein components are involved in their assembly. We recently characterized the molecular architecture of the centrosomal P4.1-associated protein (CPAP), which is crucial for controlling the centriolar cylinder length. Here, we review the remarkable architecture of the C-terminal domain of CPAP, termed the G-box, which comprises a single, entirely solvent exposed, antiparallel β-sheet. Molecular dynamics simulations support the stability of the G-box domain even in the face of truncations or amino acid substitutions. The similarity of the G-box domain to amyloids (or amyloid precursors) is strengthened by its oligomeric arrangement to form continuous fibrils. G-box fibrils were observed in crystals as well as in solution and are also supported by simulations. We conclude that the G-box domain may well represent the best analogue currently available for studies of exposed β-sheets, unencumbered by additional structural elements or severe aggregations problems.
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, U.K.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Cutts
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, U.K.
authors.forename: Alison
authors.initials: A
authors.lastname: Inglis
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, U.K.
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Stansfeld
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, U.K.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Vakonakis
authors.forename: Georgios N
authors.initials: GN
authors.lastname: Hatzopoulos
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002502:Centrioles / Q000737:chemistry* / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D066263:Protein Aggregation, Pathological / Q000378:metabolism / Q000473:pathology*; D011487:Protein Conformation; D017510:Protein Folding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D040681:Structural Homology, Protein; D029961:Zebrafish Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D000682:Amyloid; C414735:CENPJ protein, human; D029721:Drosophila Proteins; D008869:Microtubule-Associated Proteins; C522063:Sas-4 protein, Drosophila; D029961:Zebrafish Proteins; C000588998:cenpj protein, zebrafish
keywords: CPAP; b-sheet; centriole; fibril; structure