The centriolar protein CPAP G-box: an amyloid fibril in a single domain. (9th October 2015)

• Record Type: Journal Article
• Authors: Cutts, Erin E.; Inglis, Alison; Stansfeld, Phillip J.; Vakonakis, Ioannis; Hatzopoulos, Georgios N.
• Is Part Of: Biochemical Society transactions. Volume 43:Number 5(2015)
• Page Start: 838
• Page End: 843
• Publication Date: 2015-10-09
• Subjects: CPAP -- centriole -- fibril -- structure -- b-sheet; Biochemistry -- Congresses; 572
• DOI: 10.1042/BST20150082
• Languages: English
• ISSNs: 0300-5127

Abstract

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.