Crystal structures of Lys-63-linked tri- and di-ubiquitin reveal a highly extended chain architecture

Proteins. 2009 Dec;77(4):753-9. doi: 10.1002/prot.22568.


The covalent attachment of different types of poly-ubiquitin chains signal different outcomes for the proteins so targeted. For example, a protein modified with Lys-48-linked poly-ubiquitin chains is targeted for proteasomal degradation, whereas Lys-63-linked chains encode nondegradative signals. The structural features that enable these different types of chains to encode different signals have not yet been fully elucidated. We report here the X-ray crystal structures of Lys-63-linked tri- and di-ubiquitin at resolutions of 2.3 and 1.9 A, respectively. The tri- and di-ubiquitin species adopt essentially identical structures. In both instances, the ubiquitin chain assumes a highly extended conformation with a left-handed helical twist; the helical chain contains four ubiquitin monomers per turn and has a repeat length of approximately 110 A. Interestingly, Lys-48 ubiquitin chains also adopt a left-handed helical structure with a similar repeat length. However, the Lys-63 architecture is much more open than that of Lys-48 chains and exposes much more of the ubiquitin surface for potential recognition events. These new crystal structures are consistent with the results of solution studies of Lys-63 chain conformation, and reveal the structural basis for differential recognition of Lys-63 versus Lys-48 chains.

Publication types

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

MeSH terms

  • Binding Sites
  • Crystallography, X-Ray
  • Dimerization
  • Humans
  • In Vitro Techniques
  • Lysine / chemistry
  • Metals / metabolism
  • Models, Molecular
  • Polyubiquitin / chemistry
  • Polyubiquitin / metabolism
  • Protein Structure, Quaternary
  • Recombinant Proteins / metabolism
  • Ubiquitin-Activating Enzymes / metabolism
  • Ubiquitins / chemistry*
  • Ubiquitins / metabolism


  • Metals
  • Recombinant Proteins
  • Ubiquitins
  • diubiquitin conjugate
  • Polyubiquitin
  • Ubiquitin-Activating Enzymes
  • Lysine