Crystal structure of the ubiquitin binding domains of rabex-5 reveals two modes of interaction with ubiquitin

Cell. 2006 Mar 24;124(6):1183-95. doi: 10.1016/j.cell.2006.02.020. Epub 2006 Feb 23.


The interaction between ubiquitinated proteins and intracellular proteins harboring ubiquitin binding domains (UBDs) is critical to a multitude of cellular processes. Here, we report that Rabex-5, a guanine nucleotide exchange factor for Rab5, binds to Ub through two independent UBDs. These UBDs determine a number of properties of Rabex-5, including its coupled monoubiquitination and interaction in vivo with ubiquitinated EGFRs. Structural and biochemical characterization of the UBDs of Rabex-5 revealed that one of them (MIU, motif interacting with ubiquitin) binds to Ub with modes superimposable to those of the UIM (ubiquitin-interacting motif):Ub interaction, although in the opposite orientation. The other UBD, RUZ (Rabex-5 ubiquitin binding zinc finger) binds to a surface of Ub centered on Asp58(Ub) and distinct from the "canonical" Ile44(Ub)-based surface. The two binding surfaces allow Ub to interact simultaneously with different UBDs, thus opening new perspectives in Ub-mediated signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Crystallography, X-Ray
  • Epidermal Growth Factor / metabolism
  • Guanine Nucleotide Exchange Factors / chemistry*
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Multiprotein Complexes / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Ubiquitin / metabolism*


  • Guanine Nucleotide Exchange Factors
  • Multiprotein Complexes
  • RABGEF1 protein, human
  • Ubiquitin
  • Epidermal Growth Factor

Associated data

  • PDB/2C7M
  • PDB/2C7N