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

Lookup NU author(s): Dr Owen Davies

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Abstract

© Gurusaran and Davies. The Linker of Nucleoskeleton and Cytoskeleton (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.

Publication metadata

Author(s): Gurusaran M, Davies OR

Publication type: Article

Publication status: Published

Journal: eLife

Year: 2021

Volume: 10

Online publication date: 04/01/2021

Acceptance date: 03/01/2021

ISSN (electronic): 2050-084X

Publisher: eLife Sciences Publications Ltd

URL: https://doi.org/10.7554/eLife.60175

DOI: 10.7554/eLife.60175

PubMed id: 33393904

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