The hinge domain of the epigenetic repressor Smchd1 adopts an unconventional homodimeric configuration

Biochem J. 2016 Mar 15;473(6):733-42. doi: 10.1042/BJ20151049. Epub 2016 Jan 5.

Abstract

The structural maintenance of chromosomes (SMC) proteins are fundamental to chromosome organization. They share a characteristic domain structure, featuring a central SMC hinge domain that is critical for forming SMC dimers and interacting with nucleic acids. The structural maintenance of chromosomes flexible hinge domain containing 1 (Smchd1) is a non-canonical member of the SMC family. Although it has been well established that Smchd1 serves crucial roles in epigenetic silencing events implicated in development and disease, much less is known about the structure and function of the Smchd1 protein. Recently, we demonstrated that the C-terminal hinge domain of Smchd1 forms a nucleic acid-binding homodimer; however, it is unclear how the protomers are assembled within the hinge homodimer and how the full-length Smchd1 protein is organized with respect to the hinge region. In the present study, by employing SAXS we demonstrate that the hinge domain of Smchd1 probably adopts an unconventional homodimeric arrangement augmented by an intermolecular coiled coil formed between the two monomers. Such a dimeric structure differs markedly from that of archetypical SMC proteins, raising the possibility that Smchd1 binds chromatin in an unconventional manner.

Keywords: X-inactivation; coiled coil; dimer; facioscapulohumeral dystrophy (FSHD); protocadherin; structural maintenance of chromosomes (SMC).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Epigenetic Repression / physiology*
  • Gene Expression Regulation / physiology*
  • HEK293 Cells
  • Humans
  • Immunoprecipitation
  • Mice
  • Models, Molecular
  • Protein Conformation
  • Protein Structure, Tertiary
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism

Substances

  • Chromosomal Proteins, Non-Histone
  • Recombinant Proteins
  • SmcHD1 protein, mouse