Structural basis for ubiquitin recognition and autoubiquitination by Rabex-5

Nat Struct Mol Biol. 2006 Mar;13(3):264-71. doi: 10.1038/nsmb1064. Epub 2006 Feb 5.


Rabex-5 is an exchange factor for Rab5, a master regulator of endosomal trafficking. Rabex-5 binds monoubiquitin, undergoes covalent ubiquitination and contains an intrinsic ubiquitin ligase activity, all of which require an N-terminal A20 zinc finger followed immediately by a helix. The structure of the N-terminal portion of Rabex-5 bound to ubiquitin at 2.5-A resolution shows that Rabex-5-ubiquitin interactions occur at two sites. The first site is a new type of ubiquitin-binding domain, an inverted ubiquitin-interacting motif, which binds with approximately 29-microM affinity to the canonical Ile44 hydrophobic patch on ubiquitin. The second is a diaromatic patch on the A20 zinc finger, which binds with approximately 22-microM affinity to a polar region centered on Asp58 of ubiquitin. The A20 zinc-finger diaromatic patch mediates ubiquitin-ligase activity by directly recruiting a ubiquitin-loaded ubiquitin-conjugating enzyme.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites / genetics
  • Cattle
  • Conserved Sequence
  • Crystallography, X-Ray
  • DNA Mutational Analysis
  • Guanine Nucleotide Exchange Factors / chemistry*
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Conformation
  • Structure-Activity Relationship
  • Substrate Specificity
  • Thermodynamics
  • Ubiquitin / chemistry
  • Ubiquitin / metabolism*
  • Ubiquitin-Protein Ligases / metabolism
  • Zinc Fingers


  • Guanine Nucleotide Exchange Factors
  • Ubiquitin
  • Ubiquitin-Protein Ligases

Associated data

  • PDB/2FID
  • PDB/2FIF