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The centriolar protein CPAP G-box: an amyloid fibril in a single domain

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 molecula...

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Detalles Bibliográficos
Autores principales: Cutts, Erin E., Inglis, Alison, Stansfeld, Phillip J., Vakonakis, Ioannis, Hatzopoulos, Georgios N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613516/
https://www.ncbi.nlm.nih.gov/pubmed/26517891
http://dx.doi.org/10.1042/BST20150082
Descripción
Sumario: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.