Structural and dynamic independence of isopeptide-linked RanGAP1 and SUMO-1

J Biol Chem. 2004 Nov 19;279(47):49131-7. doi: 10.1074/jbc.M408705200. Epub 2004 Sep 7.

Abstract

Although sumoylation regulates a diverse and growing number of recognized biological processes, the molecular mechanisms by which the covalent attachment of the ubiquitin-like protein SUMO can alter the properties of a target protein remain to be established. To address this question, we have used NMR spectroscopy to characterize the complex of mature SUMO-1 with the C-terminal domain of human RanGAP1. Based on amide chemical shift and 15N relaxation measurements, we show that the C terminus of SUMO-1 and the loop containing the consensus sumoylation site in RanGAP1 are both conformationally flexible. Furthermore, the overall structure and backbone dynamics of each protein remain unchanged upon the covalent linkage of Lys524 in RanGAP1 to the C-terminal Gly97 of SUMO-1. Therefore, SUMO-1 and RanGAP1 behave as "beads-on-a-string," connected by a flexible isopeptide tether. Accordingly, the sumoylation-dependent interaction of RanGAP1 with the nucleoporin RanBP2 may arise through the bipartite recognition of both RanGAP1 and SUMO-1 rather than through a new binding surface induced in either individual protein upon their covalent linkage. We hypothesize that this conformational flexibility may be a general feature contributing to the recognition of ubiquitin-like modified proteins by their downstream effector machineries.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Crystallography, X-Ray
  • DNA / chemistry
  • Electrophoresis, Polyacrylamide Gel
  • Escherichia coli / metabolism
  • GTPase-Activating Proteins / chemistry*
  • GTPase-Activating Proteins / metabolism
  • Gene Library
  • Glycine / chemistry
  • HeLa Cells
  • Humans
  • Kinetics
  • Lysine / chemistry
  • Magnetic Resonance Spectroscopy
  • Models, Chemical
  • Models, Molecular
  • Peptides / chemistry*
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary
  • SUMO-1 Protein / chemistry*
  • SUMO-1 Protein / metabolism
  • Ubiquitin-Conjugating Enzymes / chemistry

Substances

  • GTPase-Activating Proteins
  • Peptides
  • RANGAP1 protein, human
  • SUMO-1 Protein
  • DNA
  • Ubiquitin-Conjugating Enzymes
  • ubiquitin-conjugating enzyme UBC9
  • Lysine
  • Glycine