Structural determinants for selective recognition of a Lys48-linked polyubiquitin chain by a UBA domain.
Although functional diversity in polyubiquitin chain signaling has been ascribed to the ability of differently linked chains to bind in a distinctive manner to effector proteins, structural models of such interactions have been lacking. Here, we use NMR to unveil the structural basis of selective recognition of Lys48-linked di- and ... tetraubiquitin chains by the UBA2 domain of hHR23A. Although the interaction of UBA2 with Lys48-linked diubiquitin involves the same hydrophobic surface on each ubiquitin unit as that utilized in monoubiquitin:UBA complexes, our results show how the "closed" conformation of Lys48-linked diubiquitin is crucial for high-affinity binding. Moreover, recognition of Lys48-linked diubiquitin involves a unique epitope on UBA, which allows the formation of a sandwich-like diubiqutin:UBA complex. Studies of the UBA-tetraubiquitin interaction suggest that this mode of UBA binding to diubiquitin is relevant for longer chains.
Mesh Terms:
Amino Acid Sequence, Binding Sites, Lysine, Magnetic Resonance Spectroscopy, Models, Molecular, Polyubiquitin, Protein Conformation, Protein Structure, Secondary, Triticum, Ubiquitin-Activating Enzymes, Ubiquitins
Amino Acid Sequence, Binding Sites, Lysine, Magnetic Resonance Spectroscopy, Models, Molecular, Polyubiquitin, Protein Conformation, Protein Structure, Secondary, Triticum, Ubiquitin-Activating Enzymes, Ubiquitins
Mol. Cell
Date: Jun. 10, 2005
PubMed ID: 15949443
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