Structural conservation of the autoinhibitory domain in SUN proteins

Biochem Biophys Res Commun. 2018 Feb 19;496(4):1337-1343. doi: 10.1016/j.bbrc.2018.02.015. Epub 2018 Feb 3.

Abstract

LINC complexes span across the nuclear envelope and are assembled by SUN and KASH proteins. SUN1 and SUN2 are the two most abundant SUN proteins in mammals. In SUN2, the predicted coiled-coil domain preceding the SUN domain forms a three-helix bundle that constitutes an autoinhibitory domain (AID) to lock down the SUN domain. Here, we found that SUN1 also contains an AID preceding the SUN domain and solved the structure of the AID-SUN tandem of SUN1. SUN1 AID also adopts a three-helix bundle conformation that interacts with the SUN domain and keeps it in an autoinhibited state. Disruptions of the interaction interface in the AID-SUN tandem restored the SUN domain activity for binding to the KASH peptide. Structural comparison further demonstrated that the autoinhibited conformations of the AID-SUN tandems from SUN1 and SUN2 are similar and the intramolecular interdomain packing in SUN1 is slightly more compact than that in SUN2 due to minor variations of the residues in the interaction interface. Thus, AID is a conserved functional domain in SUN proteins and this work provides the structural evidence to support the conversation of the AID-mediated autoinhibition of SUN proteins.

Keywords: Autoinhibition; LINC complex; SUN proteins; SUN1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Conserved Sequence
  • Intracellular Signaling Peptides and Proteins / chemistry*
  • Membrane Proteins / chemistry*
  • Membrane Proteins / ultrastructure*
  • Microtubule-Associated Proteins / chemistry*
  • Microtubule-Associated Proteins / ultrastructure*
  • Models, Chemical*
  • Molecular Docking Simulation*
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / ultrastructure*
  • Protein Binding
  • Protein Conformation
  • Protein Domains
  • Sequence Homology, Amino Acid
  • Structure-Activity Relationship

Substances

  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • SUN1 protein, human
  • SUN2 protein, human