Molecular architecture of SAS-5 enables construction of a daughter centriole
<p>In dividing cells, centrioles are duplicated once per cell cycle in a semi-conservative manner. A daughter centriole forms perpendicularly to the mother in a process templated by cartwheel-like structures. Cartwheels are found in centrioles of most eukaryotes, and are regarded as the key fa...
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | English |
| Published: |
2015
|
| Subjects: |
| _version_ | 1797080864140558336 |
|---|---|
| author | Rogala, K |
| author2 | Vakonakis, I |
| author_facet | Vakonakis, I Rogala, K |
| author_sort | Rogala, K |
| collection | OXFORD |
| description | <p>In dividing cells, centrioles are duplicated once per cell cycle in a semi-conservative manner. A daughter centriole forms perpendicularly to the mother in a process templated by cartwheel-like structures. Cartwheels are found in centrioles of most eukaryotes, and are regarded as the key factor in establishing the nine-fold symmetry of centrioles. Cartwheels comprise the self-oligomerising protein SAS-6, recruitment of which to the mother centriole is mediated by direct binding to protein SAS-5 (also known as Ana2 or STIL). Although SAS-5 is an essential protein for centriole duplication, depletion of which completely terminates centrosome-dependent cell division, its exact role in this process has remained obscure. Using X-ray crystallography and a range of biophysical techniques, we have determined the molecular architecture of SAS-5. We show that SAS-5 forms a complex oligomeric structure, mediated by two self-associating domains: a trimeric coiled coil and a novel globular dimeric Implico domain. Disruption of either domain leads to centriole duplication failure in worm embryos, indicating that large SAS-5 assemblies are necessary for function. We propose that SAS-5 provides multivalent attachment sites that are critical for promoting assembly of SAS-6 into a cartwheel, and thus centriole formation.</p> |
| first_indexed | 2024-03-07T01:06:20Z |
| format | Thesis |
| id | oxford-uuid:8b78e999-b6f6-4380-b7fb-a48c2ad59f4b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:06:20Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | oxford-uuid:8b78e999-b6f6-4380-b7fb-a48c2ad59f4b2022-03-26T22:38:18ZMolecular architecture of SAS-5 enables construction of a daughter centrioleThesishttp://purl.org/coar/resource_type/c_db06uuid:8b78e999-b6f6-4380-b7fb-a48c2ad59f4bCentrosomesStructural biologyMolecular biologyBiochemistryCentriolesBiophysicsEnglishORA Deposit2015Rogala, KVakonakis, IDeane, C<p>In dividing cells, centrioles are duplicated once per cell cycle in a semi-conservative manner. A daughter centriole forms perpendicularly to the mother in a process templated by cartwheel-like structures. Cartwheels are found in centrioles of most eukaryotes, and are regarded as the key factor in establishing the nine-fold symmetry of centrioles. Cartwheels comprise the self-oligomerising protein SAS-6, recruitment of which to the mother centriole is mediated by direct binding to protein SAS-5 (also known as Ana2 or STIL). Although SAS-5 is an essential protein for centriole duplication, depletion of which completely terminates centrosome-dependent cell division, its exact role in this process has remained obscure. Using X-ray crystallography and a range of biophysical techniques, we have determined the molecular architecture of SAS-5. We show that SAS-5 forms a complex oligomeric structure, mediated by two self-associating domains: a trimeric coiled coil and a novel globular dimeric Implico domain. Disruption of either domain leads to centriole duplication failure in worm embryos, indicating that large SAS-5 assemblies are necessary for function. We propose that SAS-5 provides multivalent attachment sites that are critical for promoting assembly of SAS-6 into a cartwheel, and thus centriole formation.</p> |
| spellingShingle | Centrosomes Structural biology Molecular biology Biochemistry Centrioles Biophysics Rogala, K Molecular architecture of SAS-5 enables construction of a daughter centriole |
| title | Molecular architecture of SAS-5 enables construction of a daughter centriole |
| title_full | Molecular architecture of SAS-5 enables construction of a daughter centriole |
| title_fullStr | Molecular architecture of SAS-5 enables construction of a daughter centriole |
| title_full_unstemmed | Molecular architecture of SAS-5 enables construction of a daughter centriole |
| title_short | Molecular architecture of SAS-5 enables construction of a daughter centriole |
| title_sort | molecular architecture of sas 5 enables construction of a daughter centriole |
| topic | Centrosomes Structural biology Molecular biology Biochemistry Centrioles Biophysics |
| work_keys_str_mv | AT rogalak moleculararchitectureofsas5enablesconstructionofadaughtercentriole |