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Structure of S5a bound to monoubiquitin provides a model for polyubiquitin recognition

J Mol Biol. 2005 May 6;348(3):727-39. doi: 10.1016/j.jmb.2005.03.007.

Abstract

Ubiquitin is a key regulatory molecule in diverse cellular events. How cells determine the outcome of ubiquitylation remains unclear; however, a likely determinant is the specificity of ubiquitin receptor proteins for polyubiquitin chains of certain length and linkage. Proteasome subunit S5a contains two ubiquitin-interacting motifs (UIMs) through which it recruits ubiquitylated substrates to the proteasome for their degradation. Here, we report the structure of S5a (196-306) alone and complexed with two monoubiquitin molecules. This construct contains the two UIMs of S5a and we reveal their different ubiquitin-binding mechanisms and provide a rationale for their unique specificities for different ubiquitin-like domains. Furthermore, we provide direct evidence that S5a (196-306) binds either K63-linked or K48-linked polyubiquitin, and in both cases prefers longer chains. On the basis of these results we present a model for how S5a and other ubiquitin-binding proteins recognize polyubiquitin.

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.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Polyubiquitin / chemistry*
  • Polyubiquitin / metabolism*
  • Proteasome Endopeptidase Complex
  • Protein Binding
  • Protein Structure, Quaternary
  • Protein Structure, Secondary*
  • RNA-Binding Proteins

Substances

  • Carrier Proteins
  • PSMD4 protein, human
  • RNA-Binding Proteins
  • Polyubiquitin
  • Proteasome Endopeptidase Complex

Associated data

  • PDB/1YX4
  • PDB/1YX5
  • PDB/1YX6