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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2015
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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. |
format | Online Article Text |
id | pubmed-4613516 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
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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