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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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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
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author Cutts, Erin E.
Inglis, Alison
Stansfeld, Phillip J.
Vakonakis, Ioannis
Hatzopoulos, Georgios N.
author_facet Cutts, Erin E.
Inglis, Alison
Stansfeld, Phillip J.
Vakonakis, Ioannis
Hatzopoulos, Georgios N.
author_sort Cutts, Erin E.
collection PubMed
description 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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spelling pubmed-46135162015-10-23 The centriolar protein CPAP G-box: an amyloid fibril in a single domain Cutts, Erin E. Inglis, Alison Stansfeld, Phillip J. Vakonakis, Ioannis Hatzopoulos, Georgios N. Biochem Soc Trans Biochemical Society Focused Meetings 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. Portland Press Ltd. 2015-10-09 2015-10-01 /pmc/articles/PMC4613516/ /pubmed/26517891 http://dx.doi.org/10.1042/BST20150082 Text en © 2015 Authors; published by Portland Press Limited
spellingShingle Biochemical Society Focused Meetings
Cutts, Erin E.
Inglis, Alison
Stansfeld, Phillip J.
Vakonakis, Ioannis
Hatzopoulos, Georgios N.
The centriolar protein CPAP G-box: an amyloid fibril in a single domain
title The centriolar protein CPAP G-box: an amyloid fibril in a single domain
title_full The centriolar protein CPAP G-box: an amyloid fibril in a single domain
title_fullStr The centriolar protein CPAP G-box: an amyloid fibril in a single domain
title_full_unstemmed The centriolar protein CPAP G-box: an amyloid fibril in a single domain
title_short The centriolar protein CPAP G-box: an amyloid fibril in a single domain
title_sort centriolar protein cpap g-box: an amyloid fibril in a single domain
topic Biochemical Society Focused Meetings
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613516/
https://www.ncbi.nlm.nih.gov/pubmed/26517891
http://dx.doi.org/10.1042/BST20150082
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