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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10320395/ https://www.ncbi.nlm.nih.gov/pubmed/37416798 http://dx.doi.org/10.3389/fcell.2023.1144277 |
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author | Gurusaran, Manickam Biemans, Jelle J. Wood, Christopher W. Davies, Owen R. |
author_facet | Gurusaran, Manickam Biemans, Jelle J. Wood, Christopher W. Davies, Owen R. |
author_sort | Gurusaran, Manickam |
collection | PubMed |
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 | Online Article Text |
id | pubmed-10320395 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-103203952023-07-06 Molecular insights into LINC complex architecture through the crystal structure of a luminal trimeric coiled-coil domain of SUN1 Gurusaran, Manickam Biemans, Jelle J. Wood, Christopher W. Davies, Owen R. Front Cell Dev Biol Cell and Developmental Biology 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. Frontiers Media S.A. 2023-06-21 /pmc/articles/PMC10320395/ /pubmed/37416798 http://dx.doi.org/10.3389/fcell.2023.1144277 Text en Copyright © 2023 Gurusaran, Biemans, Wood and Davies. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Gurusaran, Manickam Biemans, Jelle J. Wood, Christopher W. Davies, Owen R. Molecular insights into LINC complex architecture through the crystal structure of a luminal trimeric coiled-coil domain of SUN1 |
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 | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10320395/ https://www.ncbi.nlm.nih.gov/pubmed/37416798 http://dx.doi.org/10.3389/fcell.2023.1144277 |
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