A Disulfide Bond Is Required for the Transmission of Forces through SUN-KASH Complexes

Zeinab Jahed; Hengameh Shams; Mohammad R K Mofrad

doi:10.1016/j.bpj.2015.06.057

A Disulfide Bond Is Required for the Transmission of Forces through SUN-KASH Complexes

Biophys J. 2015 Aug 4;109(3):501-9. doi: 10.1016/j.bpj.2015.06.057.

Authors

Zeinab Jahed¹, Hengameh Shams¹, Mohammad R K Mofrad²

Affiliations

¹ Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California Berkeley, Berkeley, California.
² Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California Berkeley, Berkeley, California; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California. Electronic address: mofrad@berkeley.edu.

Abstract

Numerous biological functions of a cell, including polarization, differentiation, division, and migration, rely on its ability to endure mechanical forces generated by the cytoskeleton on the nucleus. Coupling of the cytoskeleton and nucleoskeleton is ultimately mediated by LINC complexes that are formed via a strong interaction between SUN- and KASH-domain-containing proteins in the nuclear envelope. These complexes are mechanosensitive and essential for the transmission of forces between the cytoskeleton and nucleoskeleton, and the progression of cellular mechanotransduction. Herein, using molecular dynamics, we examine the effect of tension on the human SUN2-KASH2 complex and show that it is remarkably stable under physiologically relevant tensile forces and large strains. However, a covalent disulfide bond between two highly conserved cysteine residues of SUN2 and KASH2 is crucial for the stability of this interaction and the transmission of forces through the complex.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Disulfides / chemistry*
Humans
Intracellular Signaling Peptides and Proteins / chemistry*
Intracellular Signaling Peptides and Proteins / metabolism
Mechanotransduction, Cellular
Membrane Proteins / chemistry*
Membrane Proteins / metabolism
Molecular Dynamics Simulation*
Molecular Sequence Data
Nuclear Proteins / chemistry*
Nuclear Proteins / metabolism
Protein Binding

Substances

Disulfides
Intracellular Signaling Peptides and Proteins
Membrane Proteins
Nuclear Proteins
SUN2 protein, human