Structural determinants for the binding of ubiquitin-like domains to the proteasome.
HHR23A, a protein implicated in nucleotide excision repair, belongs to a class of proteins containing both a ubiquitin-like (Ubl) domain and one or more ubiquitin-associated (UBA) domains, suggesting a role in the ubiquitin-proteasome pathway as well. The Ubl domain binds with high affinity to the second ubiquitin-interacting motif (UIM) of ... the S5a subunit of the proteasome. Here we present the solution structures of the HHR23A Ubl domain, the second UIM of S5a (UIM-2), and the Ubl:S5a-UIM-2 complex. The HHR23A Ubl domain is structurally similar to ubiquitin. The S5a UIM forms an alpha-helix with an unexpected hairpin loop that contributes to the binding interface with Ubl. The molecular determinants of the Ubl-proteasome interaction are revealed by analysis of the structures, chemical shift mapping, mutant binding studies and sequence conservation.
Mesh Terms:
Amino Acid Sequence, Animals, Binding Sites, Conserved Sequence, Humans, Magnetic Resonance Spectroscopy, Models, Molecular, Molecular Sequence Data, Peptide Hydrolases, Proteasome Endopeptidase Complex, Protein Conformation, Protein Structure, Secondary, Protein Subunits, Recombinant Proteins, Sequence Alignment, Sequence Homology, Amino Acid, Ubiquitin
Amino Acid Sequence, Animals, Binding Sites, Conserved Sequence, Humans, Magnetic Resonance Spectroscopy, Models, Molecular, Molecular Sequence Data, Peptide Hydrolases, Proteasome Endopeptidase Complex, Protein Conformation, Protein Structure, Secondary, Protein Subunits, Recombinant Proteins, Sequence Alignment, Sequence Homology, Amino Acid, Ubiquitin
EMBO J.
Date: Sep. 15, 2003
PubMed ID: 12970176
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