Molecular insights into LINC complex architecture through the crystal structure of a luminal trimeric coiled-coil domain of SUN1
The LINC complex, consisting of interacting SUN and KASH proteins, mechanically couples nuclear contents to the cytoskeleton. In meiosis, the LINC complex transmits microtubule-generated forces to chromosome ends, driving the rapid chromosome movements that are necessary for synapsis and crossing ov...
| الحاوية / القاعدة: | Frontiers in Cell and Developmental Biology |
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| المؤلفون الرئيسيون: | , , , |
| التنسيق: | مقال |
| اللغة: | الإنجليزية |
| منشور في: |
Frontiers Media S.A.
2023-06-01
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| الموضوعات: | |
| الوصول للمادة أونلاين: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1144277/full |
| _version_ | 1852701720661983232 |
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| author | Manickam Gurusaran Jelle J. Biemans Christopher W. Wood Owen R. Davies |
| author_facet | Manickam Gurusaran Jelle J. Biemans Christopher W. Wood Owen R. Davies |
| author_sort | Manickam Gurusaran |
| collection | DOAJ |
| container_title | Frontiers in Cell and Developmental Biology |
| description | The LINC complex, consisting of interacting SUN and KASH proteins, mechanically couples nuclear contents to the cytoskeleton. In meiosis, the LINC complex transmits microtubule-generated forces to chromosome ends, driving the rapid chromosome movements that are necessary for synapsis and crossing over. In somatic cells, it defines nuclear shape and positioning, and has a number of specialised roles, including hearing. Here, we report the X-ray crystal structure of a coiled-coiled domain of SUN1’s luminal region, providing an architectural foundation for how SUN1 traverses the nuclear lumen, from the inner nuclear membrane to its interaction with KASH proteins at the outer nuclear membrane. In combination with light and X-ray scattering, molecular dynamics and structure-directed modelling, we present a model of SUN1’s entire luminal region. This model highlights inherent flexibility between structured domains, and raises the possibility that domain-swap interactions may establish a LINC complex network for the coordinated transmission of cytoskeletal forces. |
| format | Article |
| id | doaj-art-36e24ef53b0d48e19c8a3773fdffbf45 |
| institution | Directory of Open Access Journals |
| issn | 2296-634X |
| language | English |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| spelling | doaj-art-36e24ef53b0d48e19c8a3773fdffbf452025-08-19T21:20:14ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-06-011110.3389/fcell.2023.11442771144277Molecular insights into LINC complex architecture through the crystal structure of a luminal trimeric coiled-coil domain of SUN1Manickam Gurusaran0Jelle J. Biemans1Christopher W. Wood2Owen R. Davies3Wellcome Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh, Scotland, United KingdomWellcome Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh, Scotland, United KingdomInstitute of Quantitative Biology, Biochemistry and Biotechnology, University of Edinburgh, Edinburgh, Scotland, United KingdomWellcome Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh, Scotland, United KingdomThe LINC complex, consisting of interacting SUN and KASH proteins, mechanically couples nuclear contents to the cytoskeleton. In meiosis, the LINC complex transmits microtubule-generated forces to chromosome ends, driving the rapid chromosome movements that are necessary for synapsis and crossing over. In somatic cells, it defines nuclear shape and positioning, and has a number of specialised roles, including hearing. Here, we report the X-ray crystal structure of a coiled-coiled domain of SUN1’s luminal region, providing an architectural foundation for how SUN1 traverses the nuclear lumen, from the inner nuclear membrane to its interaction with KASH proteins at the outer nuclear membrane. In combination with light and X-ray scattering, molecular dynamics and structure-directed modelling, we present a model of SUN1’s entire luminal region. This model highlights inherent flexibility between structured domains, and raises the possibility that domain-swap interactions may establish a LINC complex network for the coordinated transmission of cytoskeletal forces.https://www.frontiersin.org/articles/10.3389/fcell.2023.1144277/fullLINC complexnuclear envelopeSUN1KASH5X-ray crystallographymolecular dynamics |
| spellingShingle | Manickam Gurusaran Jelle J. Biemans Christopher W. Wood Owen R. Davies Molecular insights into LINC complex architecture through the crystal structure of a luminal trimeric coiled-coil domain of SUN1 LINC complex nuclear envelope SUN1 KASH5 X-ray crystallography molecular dynamics |
| title | Molecular insights into LINC complex architecture through the crystal structure of a luminal trimeric coiled-coil domain of SUN1 |
| title_full | Molecular insights into LINC complex architecture through the crystal structure of a luminal trimeric coiled-coil domain of SUN1 |
| title_fullStr | Molecular insights into LINC complex architecture through the crystal structure of a luminal trimeric coiled-coil domain of SUN1 |
| title_full_unstemmed | Molecular insights into LINC complex architecture through the crystal structure of a luminal trimeric coiled-coil domain of SUN1 |
| title_short | Molecular insights into LINC complex architecture through the crystal structure of a luminal trimeric coiled-coil domain of SUN1 |
| title_sort | molecular insights into linc complex architecture through the crystal structure of a luminal trimeric coiled coil domain of sun1 |
| topic | LINC complex nuclear envelope SUN1 KASH5 X-ray crystallography molecular dynamics |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1144277/full |
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