Two-sided ubiquitin binding explains specificity of the TAB2 NZF domain

Nat Struct Mol Biol. 2009 Dec;16(12):1328-30. doi: 10.1038/nsmb.1731. Epub 2009 Nov 22.

Abstract

The protein kinase TAK1 is activated by binding to Lys63 (K63)-linked ubiquitin chains through its subunit TAB2. Here we analyze crystal structures of the TAB2 NZF domain bound to Lys63-linked di- and triubiquitin, revealing that TAB2 binds adjacent ubiquitin moieties via two distinct binding sites. The conformational constraints imposed by TAB2 on a Lys63 dimer cannot be adopted by linear chains, explaining why TAK1 cannot be activated by linear ubiquitination events.

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry*
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Substrate Specificity
  • Ubiquitin / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • TAB2 protein, human
  • Ubiquitin