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Solution structure of Vps27 UIM–ubiquitin complex important for endosomal sorting and receptor downregulation
Author(s) -
Swanson Kurt A.,
Kang Richard S.,
Stamenova Svetoslava D.,
Hicke Linda,
Radhakrishnan Ishwar
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg471
Subject(s) - endocytic cycle , ubiquitin , biology , endosome , internalization , escrt , microbiology and biotechnology , protein sorting signals , protein targeting , lysosome , protein subunit , transport protein , membrane protein , ubiquitins , plasma protein binding , ubiquitin ligase , endocytosis , biochemistry , peptide sequence , receptor , signal peptide , membrane , gene , intracellular , enzyme
Monoubiquitylation is a well‐characterized signal for the internalization and sorting of integral membrane proteins to distinct cellular organelles. Recognition and transmission of monoubiquitin signals is mediated by a variety of ubiquitin‐binding motifs such as UIM, UBA, UEV, VHS and CUE in endocytic proteins. The yeast Vps27 protein requires two UIMs for efficient interactions with ubiquitin and for sorting cargo into multivesicular bodies. Here we show that the individual UIMs of Vps27 exist as autonomously folded α‐helices that bind ubiquitin independently, non‐cooperatively and with modest affinity. The Vps27 N‐terminal UIM engages the Leu8–Ile44–Val70 hydrophobic patch of ubiquitin through a helical surface conserved in UIMs of diverse proteins, including that of the S5a proteasomal regulatory subunit. The Leu8–Ile44–Val70 ubiquitin surface is also the site of interaction for CUE and UBA domains in endocytic proteins, consistent with the view that ubiquitin‐ binding endocytic proteins act serially on the same monoubiquitylated cargo during transport from cell surface to the lysosome.