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.
Structural determinants for selective recognition of a Lys48-linked polyubiquitin chain by a UBA domain.,Varadan R, Assfalg M, Raasi S, Pickart C, Fushman D Mol Cell. 2005 Jun 10;18(6):687-98. PMID:15949443[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
↑ Varadan R, Assfalg M, Raasi S, Pickart C, Fushman D. Structural determinants for selective recognition of a Lys48-linked polyubiquitin chain by a UBA domain. Mol Cell. 2005 Jun 10;18(6):687-98. PMID:15949443 doi:10.1016/j.molcel.2005.05.013
