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PDBsum entry 1uzx
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Transport protein
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PDB id
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1uzx
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structural insights into endosomal sorting complex required for transport (escrt-I) recognition of ubiquitinated proteins.
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Authors
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H.Teo,
D.B.Veprintsev,
R.L.Williams.
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Ref.
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J Biol Chem, 2004,
279,
28689-28696.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 4.
FIG. 4. Stereo representation of the detailed interactions
between the UEV and the bound Ub. Residues in direct contact
(closer than 4.0 Å) between the Vps23 UEV (yellow) and the
Ub (magenta) are labeled. Direct hydrogen bonds between the UEV
and the Ub are indicated as dashed lines.
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Figure 6.
FIG. 6. A comparison of the yeast and human ESCRT-I UEVs.
Left, representations of the Vps23 UEV/Ub complex; right,
representations of the Tsg101 UEV complex with a PTAP-peptide
from the HIV-1 p6 protein (65). The vestigial active-site loop
is colored cyan and the  -hairpin tongue and lip
are colored red. The Ub bound to the Vps23 UEV is colored green,
and the PTAP peptide bound to Tsg101 is colored black.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2004,
279,
28689-28696)
copyright 2004.
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