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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...

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Autores principales: Gurusaran, Manickam, Biemans, Jelle J., Wood, Christopher W., Davies, Owen R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
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.
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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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