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PDBsum entry 2g3q
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Endocytosis/signaling protein
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PDB id
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2g3q
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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 basis for monoubiquitin recognition by the ede1 uba domain.
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Authors
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K.A.Swanson,
L.Hicke,
I.Radhakrishnan.
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Ref.
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J Mol Biol, 2006,
358,
713-724.
[DOI no: ]
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PubMed id
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Abstract
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Monoubiquitination is a general mechanism for downregulating the activity of
cell surface receptors by consigning these proteins for lysosome-mediated
degradation through the endocytic pathway. The yeast Ede1 protein functions at
the internalization step of endocytosis and binds monoubiquitinated proteins
through a ubiquitin associated (UBA) domain. UBA domains are found in a broad
range of cellular proteins but previous studies have suggested that the mode of
ubiquitin recognition might not be universally conserved. Here we present the
solution structure of the Ede1 UBA domain in complex with monoubiquitin. The
Ede1 UBA domain forms a three-helix bundle structure and binds ubiquitin through
a largely hydrophobic surface in a manner reminiscent of the Dsk2 UBA and the
remotely homologous Cue2 CUE domains, for which high-resolution structures have
been described. However, the interaction is dissimilar to the molecular models
proposed for the hHR23A UBA domains bound to either monoubiquitin or
Lys48-linked diubiquitin. Our mutational analyses of the Ede1 UBA
domain-ubiquitin interaction reveal several key affinity determinants and,
unexpectedly, a negative affinity determinant in the wild-type Ede1 protein,
implying that high-affinity interactions may not be the sole criterion for
optimal function of monoubiquitin-binding endocytic proteins.
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Figure 2.
Figure 2. Solution structure of the Ede1 UBA
domain–ubiquitin complex. (a) Stereo views of the C^α trace
following a best fit superposition of the backbone atoms in
well-ordered regions (1342–1378 of Ede1 and 1–70 of
ubiquitin) in the ensemble of 20 NMR structures. The Ede1 UBA
domain is colored light blue, whereas ubiquitin is shown in
green. (b) Stereo views of the representative structure from the
ensemble shown in a ribbon representation.
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Figure 5.
Figure 5. Structural comparison of the monoubiquitin
binding modes of the Ede1 UBA, Cue2 CUE^14 and Dsk2 UBA^13
domains. (a) A structure-guided multiple sequence alignment of
the Ede1 UBA, Dsk2 UBA and Cue2 CUE domains. Residues in helical
regions are shown in uppercase and in bold font for clarity.
Residues constituting the hydrophobic cores of the respective
domains are shaded in yellow, whereas those that interact with
ubiquitin in the respective complexes are shaded in light blue.
(b) Comparison of the Ede1 UBA domain–ubiquitin (light blue)
and Dsk2 UBA domain–ubiquitin (purple) complexes following a
best-fit superposition of the backbone atoms of residues 1–70
of ubiquitin. (c) Ribbon diagrams of the Ede1 UBA domain (light
blue) and Cue2 CUE domain (magenta)–monoubiquitin complexes
following a best-fit superposition of the polypeptide backbone
encompassing residues 1–70 of ubiquitin.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2006,
358,
713-724)
copyright 2006.
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