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PDBsum entry 3ldz
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Protein transport
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PDB id
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3ldz
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References listed in PDB file
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Key reference
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Title
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Vhs domains of escrt-0 cooperate in high-Avidity binding to polyubiquitinated cargo.
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Authors
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X.Ren,
J.H.Hurley.
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Ref.
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Embo J, 2010,
29,
1045-1054.
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PubMed id
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Abstract
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VHS (Vps27, Hrs, and STAM) domains occur in ESCRT-0 subunits Hrs and STAM, GGA
adapters, and other trafficking proteins. The structure of the STAM VHS
domain-ubiquitin complex was solved at 2.6 A resolution, revealing that
determinants for ubiquitin recognition are conserved in nearly all VHS domains.
VHS domains from all classes of VHS-domain containing proteins in yeast and
humans, including both subunits of ESCRT-0, bound ubiquitin in vitro. ESCRTs
have been implicated in the sorting of Lys63-linked polyubiquitinated cargo.
Intact human ESCRT-0 binds Lys63-linked tetraubiquitin 50-fold more tightly than
monoubiquitin, though only 2-fold more tightly than Lys48-linked tetraubiquitin.
The gain in affinity is attributed to the cooperation of flexibly connected VHS
and UIM motifs of ESCRT-0 in avid binding to the polyubiquitin chain. Mutational
analysis of all the five ubiquitin-binding sites in yeast ESCRT-0 shows that
cooperation between them is required for the sorting of the Lys63-linked
polyubiquitinated cargo Cps1 to the vacuole.
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