Structure of the small ubiquitin-like modifier (SUMO)-interacting motif of MBD1-containing chromatin-associated factor 1 bound to SUMO-3

J Biol Chem. 2008 Dec 19;283(51):35966-75. doi: 10.1074/jbc.M802528200. Epub 2008 Oct 7.

Abstract

Post-translational modification by small ubiquitin-like modifier (SUMO) proteins has been implicated in the regulation of a variety of cellular events. The functions of sumoylation are often mediated by downstream effector proteins harboring SUMO-interacting motifs (SIMs) that are composed of a hydrophobic core and a stretch of acidic residues. MBD1-containing chromatin-associated factor 1 (MCAF1), a transcription repressor, interacts with SUMO-2/3 and SUMO-1, with a preference for SUMO-2/3. We used NMR spectroscopy to solve the solution structure of the SIM of MCAF1 bound to SUMO-3. The hydrophobic core of the SIM forms a parallel beta-sheet pairing with strand beta2 of SUMO-3, whereas its C-terminal acidic stretch seems to mediate electrostatic interactions with a surface area formed by basic residues of SUMO-3. The significance of these electrostatic interactions was shown by mutations of both SUMO-3 and MCAF1. The present structural and biochemical data suggest that the acidic stretch of the SIM of MCAF1 plays an important role in the binding to SUMO-3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs / physiology
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Mutation
  • Nuclear Magnetic Resonance, Biomolecular / methods
  • Protein Binding / physiology
  • Protein Processing, Post-Translational / physiology*
  • Protein Structure, Quaternary / physiology
  • Repressor Proteins
  • Static Electricity
  • Transcription Factors / chemistry*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Ubiquitins / chemistry*
  • Ubiquitins / genetics
  • Ubiquitins / metabolism

Substances

  • ATF7IP protein, human
  • Repressor Proteins
  • SUMO3 protein, human
  • Transcription Factors
  • Ubiquitins

Associated data

  • PDB/2RPQ