A molecular mechanism for LINC complex branching by structurally diverse SUN-KASH 6:6 assemblies

  1. Manickam Gurusaran
  2. Owen Richard Davies  Is a corresponding author
  1. Newcastle University, United Kingdom

Abstract

The LINC complex mechanically couples cytoskeletal and nuclear components across the nuclear envelope to fulfil a myriad of cellular functions, including nuclear shape and positioning, hearing and meiotic chromosome movements. The canonical model is that 3:3 interactions between SUN and KASH proteins underlie the nucleocytoskeletal linkages provided by the LINC complex. Here, we provide crystallographic and biophysical evidence that SUN-KASH is a constitutive 6:6 complex in which two constituent 3:3 complexes interact head-to-head. A common SUN-KASH topology is achieved through structurally diverse 6:6 interaction mechanisms by distinct KASH proteins, including zinc-coordination by Nesprin-4. The SUN-KASH 6:6 interface provides a molecular mechanism for the establishment of integrative and distributive connections between 3:3 structures within a branched LINC complex network. In this model, SUN-KASH 6:6 complexes act as nodes for force distribution and integration between adjacent SUN and KASH molecules, enabling the coordinated transduction of large forces across the nuclear envelope.

Data availability

Crystallographic structure factors and atomic coordinates have been deposited in the Protein Data Bank (PDB) under accession numbers 6R15, 6R16 and 6R2I, and raw diffraction data have been uploaded to https://proteindiffraction.org/. SEC-SAXS data have been deposited in the Small Angle Scattering Biological Data Bank (https://www.sasbdb.org/) under accession numbers SASDJC5, SASDJD5, SASDJE5 and SASDJF5. Uncropped gel images relating to Figures 4b and 5a are available in source data files.

The following data sets were generated

Article and author information

Author details

  1. Manickam Gurusaran

    Cell Division Biology Group, Biosciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6603-3118
  2. Owen Richard Davies

    Cell Division Biology Group, Biosciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
    For correspondence
    owen.davies@ed.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3806-5403

Funding

Wellcome Trust and Royal Society (104158/Z/14/Z)

  • Owen Richard Davies

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Megan C King, Yale School of Medicine, United States

Publication history

  1. Received: June 18, 2020
  2. Accepted: January 3, 2021
  3. Accepted Manuscript published: January 4, 2021 (version 1)
  4. Version of Record published: January 11, 2021 (version 2)

Copyright

© 2021, Gurusaran & Davies

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Manickam Gurusaran
  2. Owen Richard Davies
(2021)
A molecular mechanism for LINC complex branching by structurally diverse SUN-KASH 6:6 assemblies
eLife 10:e60175.
https://doi.org/10.7554/eLife.60175
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