Molecular insights into LINC complex architecture through the crystal structure of a luminal trimeric coiled-coil domain of SUN1

Frontiers in Cell and Developmental Biology

Cell and Developmental Biology

Christopher W. Wood¹  Jelle J. Biemans²  Manickam Gurusaran²  Owen R. Davies² 

[1] Institute of Quantitative Biology, Biochemistry and Biotechnology, University of Edinburgh, Edinburgh, Scotland, United Kingdom;Wellcome Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh, Scotland, United Kingdom;

关键词: LINC complex;    nuclear envelope;    SUN1;    KASH5;    X-ray crystallography;    molecular dynamics;    biophysics;   

DOI  :  10.3389/fcell.2023.1144277

 received in 2023-01-14, accepted in 2023-06-09,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Gurusaran, Biemans, Wood and Davies.