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PDBsum entry 1fbv
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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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Structure of a c-Cbl-Ubch7 complex: ring domain function in ubiquitin-Protein ligases.
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Authors
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N.Zheng,
P.Wang,
P.D.Jeffrey,
N.P.Pavletich.
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Ref.
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Cell, 2000,
102,
533-539.
[DOI no: ]
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PubMed id
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Abstract
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Ubiquitin-protein ligases (E3s) regulate diverse cellular processes by mediating
protein ubiquitination. The c-Cbl proto-oncogene is a RING family E3 that
recognizes activated receptor tyrosine kinases, promotes their ubiquitination by
a ubiquitin-conjugating enzyme (E2) and terminates signaling. The crystal
structure of c-Cbl bound to a cognate E2 and a kinase peptide shows how the RING
domain recruits the E2. A comparison with a HECT family E3-E2 complex indicates
that a common E2 motif is recognized by the two E3 families. The structure
reveals a rigid coupling between the peptide binding and the E2 binding domains
and a conserved surface channel leading from the peptide to the E2 active site,
suggesting that RING E3s may function as scaffolds that position the substrate
and the E2 optimally for ubiquitin transfer.
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Figure 4.
Figure 4. The RING Domain of c-Cbl and the HECT Domain of
E6AP Recognize the Same Structural Elements of UbcH7The H1
helix, L1, and L2 loops of UbcH7 are colored in green, red, and
yellow, respectively. Portions of the molecular surfaces of the
RING domain of c-Cbl (left) and the HECT domain of E6AP (right)
are shown as a white net. The Phe-63 residue of UbcH7 inserts
its side chain into a groove formed by the E3 in both cases.
(Prepared with the program GRASP; [25])
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Figure 5.
Figure 5. c-Cbl Has a Conserved Surface Channel Leading
from the Peptide to the E2 Active SiteOne side of the
c-Cbl–UbcH7 complex is characterized by a surface channel
formed by residues that are solvent exposed and generally
conserved (Lys-78, Asn-79, Ser-80, Arg-148, Arg-149, Lys-153,
Asp-275, Glu-276, Lys-278, Ala-279, Arg-280, Gln-267, Leu-370,
Glu-373, Met-374, and Lys-382). The molecular surfaces of c-Cbl
and UbcH7 are colored in green and blue, respectively. On c-Cbl,
the surface of the residues completely conserved in human c-Cbl,
human cbl-b, human cbl-c, C. elegans sli-1, and Drosophila cbl
are colored in yellow. The surface of the UbcH7 active-site
cysteine is colored orange. The channel is outlined by three
solid red lines. The right panel shows that the molecular
surface of the complex opposite to the side containing the
channel is not conserved. The view on the left has an
orientation similar to that of Figure 1A.
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The above figures are
reprinted
by permission from Cell Press:
Cell
(2000,
102,
533-539)
copyright 2000.
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