1uzx
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A COMPLEX OF THE VPS23 UEV WITH UBIQUITIN
OverviewOverview
The endosomal sorting complex required for transport (ESCRT-I) is a, 350-kDa complex of three proteins, Vps23, Vps28, and Vps37. The N-terminal, ubiquitin-conjugating enzyme E2 variant (UEV) domain of Vps23 is required, for sorting ubiquitinated proteins into the internal vesicles of, multivesicular bodies. UEVs are homologous to E2 ubiquitin ligases but, lack the conserved cysteine residue required for catalytic activity. The, crystal structure of the yeast Vps23 UEV in a complex with ubiquitin (Ub), shows the detailed interactions made with the bound Ub. Compared with the, solution structure of the Tsg101 UEV (the human homologue of Vps23) in the, absence of Ub, two loops that are conserved among the ESCRT-I UEVs move, toward each other to grip the Ub in a pincer-like grasp. The contacts with, the UEV encompass two adjacent patches on the surface of the Ub, one, containing several hydrophobic residues, including Ile-8(Ub), Ile-44(Ub), and Val-70(Ub), and the second containing a hydrophilic patch including, residues Asn-60(Ub), Gln-62(Ub), Glu-64(Ub). The hydrophobic Ub patch, interacting with the Vps23 UEV overlaps the surface of Ub interacting with, the Vps27 ubiquitin-interacting motif, suggesting a sequential model for, ubiquitinated cargo binding by these proteins. In contrast, the, hydrophilic patch encompasses residues uniquely interacting with the, ESCRT-I UEV. The structure provides a detailed framework for design of, mutants that can specifically affect ESCRT-I-dependent sorting of, ubiquitinated cargo without affecting Vps27-mediated delivery of cargo to, endosomes.
About this StructureAbout this Structure
1UZX is a Protein complex structure of sequences from Bos taurus and Saccharomyces cerevisiae with SO4 and MES as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
Structural insights into endosomal sorting complex required for transport (ESCRT-I) recognition of ubiquitinated proteins., Teo H, Veprintsev DB, Williams RL, J Biol Chem. 2004 Jul 2;279(27):28689-96. Epub 2004 Mar 24. PMID:15044434
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