Structural basis for distinct roles of Lys63- and Lys48-linked polyubiquitin chains

Genes Cells. 2004 Oct;9(10):865-75. doi: 10.1111/j.1365-2443.2004.00780.x.


Ubiquitination, a modification in which single or multiple ubiquitin molecules are attached to a protein, serves as a signalling function that controls a wide variety of cellular processes. To date, two major forms of polyubiquitin chain have been functionally characterized, in which the isopeptide bond linkages involve Lys48 or Lys63. Lys48-linked polyubiquitin tagging is mostly used to target proteins for degradation by the proteasome, whereas Lys63-linked polyubiquitination has been linked to numerous cellular events that do not rely on degradative signalling via the proteasome. Apparently linkage-specific conformations of polyubiquitin chains are important for these cellular functions, but the structural bases distinguishing Lys48- and Lys63-linked chains remain elusive. Here, we report NMR and small-angle X-ray scattering (SAXS) studies on the intersubunit interfaces and conformations of Lys63- and Lys48-linked di- and tetraubiquitin chains. Our results indicate that, in marked contrast to Lys48-linked chains, Lys63-linked chains are elongated molecules with no stable non-covalent intersubunit interfaces and thus adopt a radically different conformation from that of Lys48-linked chains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Lysine / metabolism*
  • Magnetic Resonance Spectroscopy
  • Polyubiquitin / chemistry*
  • Polyubiquitin / metabolism
  • Protein Conformation


  • Polyubiquitin
  • Lysine