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.
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October 2015
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Review Article|
October 09 2015
The centriolar protein CPAP G-box: an amyloid fibril in a single domain
Erin E. Cutts;
Erin E. Cutts
*Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, U.K.
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Alison Inglis;
Alison Inglis
*Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, U.K.
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Phillip J. Stansfeld;
Phillip J. Stansfeld
*Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, U.K.
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Ioannis Vakonakis;
Ioannis Vakonakis
*Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, U.K.
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Georgios N. Hatzopoulos
2To whom correspondence should be addressed (emailgeorgios.hatzopoulos@epfl.ch.)
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Publisher: Portland Press Ltd
Received:
April 20 2015
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2015 Authors; published by Portland Press Limited
2015
Biochem Soc Trans (2015) 43 (5): 838–843.
Article history
Received:
April 20 2015
Citation
Erin E. Cutts, Alison Inglis, Phillip J. Stansfeld, Ioannis Vakonakis, Georgios N. Hatzopoulos; The centriolar protein CPAP G-box: an amyloid fibril in a single domain. Biochem Soc Trans 1 October 2015; 43 (5): 838–843. doi: https://doi.org/10.1042/BST20150082
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