Structure of Sad1-UNC84 homology (SUN) domain defines features of molecular bridge in nuclear envelope

J Biol Chem. 2012 Feb 17;287(8):5317-26. doi: 10.1074/jbc.M111.304543. Epub 2011 Dec 14.

Abstract

The SUN (Sad1-UNC-84 homology) domain is conserved in a number of nuclear envelope proteins involved in nuclear migration, meiotic telomere tethering, and antiviral responses. The LINC (linker of nucleoskeleton and cytoskeleton) complex, formed by the SUN and the nesprin proteins at the nuclear envelope, serves as a mechanical linkage across the nuclear envelope. Here we report the crystal structure of the SUN2 protein SUN domain, which reveals a homotrimer. The SUN domain is sufficient to mediate binding to the KASH (Klarsicht, ANC-1, and Syne homology) domain of nesprin 2, and the regions involved in the interaction have been identified. Binding of the SUN domain to the KASH domain is abolished by deletion of a region important for trimerization or by point mutations associated with nuclear migration failure. We propose a model of the LINC complex, where the SUN and the KASH domains form a higher ordered oligomeric network in the nuclear envelope. These findings provide the structural basis for understanding the function and the regulation of the LINC complex.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Crystallography, X-Ray
  • Cytoskeleton / metabolism
  • HEK293 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / chemistry*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism*
  • Microfilament Proteins / chemistry
  • Microfilament Proteins / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / metabolism
  • Nuclear Envelope / chemistry*
  • Nuclear Envelope / metabolism*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism
  • Protein Multimerization
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary

Substances

  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Microfilament Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • SUN2 protein, human
  • SYNE2 protein, human

Associated data

  • PDB/3UNP