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PDBsum entry 2c7m
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Protein binding
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PDB id
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2c7m
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the ubiquitin binding domains of rabex-5 reveals two modes of interaction with ubiquitin.
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Authors
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L.Penengo,
M.Mapelli,
A.G.Murachelli,
S.Confalonieri,
L.Magri,
A.Musacchio,
P.P.Di fiore,
S.Polo,
T.R.Schneider.
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Ref.
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Cell, 2006,
124,
1183-1195.
[DOI no: ]
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PubMed id
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Abstract
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The interaction between ubiquitinated proteins and intracellular proteins
harboring ubiquitin binding domains (UBDs) is critical to a multitude of
cellular processes. Here, we report that Rabex-5, a guanine nucleotide exchange
factor for Rab5, binds to Ub through two independent UBDs. These UBDs determine
a number of properties of Rabex-5, including its coupled monoubiquitination and
interaction in vivo with ubiquitinated EGFRs. Structural and biochemical
characterization of the UBDs of Rabex-5 revealed that one of them (MIU, motif
interacting with ubiquitin) binds to Ub with modes superimposable to those of
the UIM (ubiquitin-interacting motif):Ub interaction, although in the opposite
orientation. The other UBD, RUZ (Rabex-5 ubiquitin binding zinc finger) binds to
a surface of Ub centered on Asp58(Ub) and distinct from the
"canonical" Ile44(Ub)-based surface. The two binding surfaces allow Ub
to interact simultaneously with different UBDs, thus opening new perspectives in
Ub-mediated signaling.
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Figure 3.
Figure 3. Overview of the Structure
(A) Secondary
structure diagram (left) and surface representation (right) of
two molecules of RUZ-MIU (yellow and orange) in complex with two
molecules of Ub (light green and dark green). The Zn^2+ ions of
Rabex-5[2–74] are drawn as orange spheres.
(B)
Superposition of two molecules of RUZ-MIU, orange and yellow.
Residues 40–64[Rbx] are shown as a helix, while for residues
17–39[Rbx] the backbone trace is indicated by a tube; Zn^2+
ions are drawn as spheres.
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Figure 5.
Figure 5. The MIU:Ub Complex Resembles the UIM:Ub Complex
(A) Structures of the Rabex-5-MIU:Ub (yellow and green) and
the Vps27-UIM:Ub (red and green) complexes.
(B) 2F[obs] −
1F[calc] difference electron density contoured at the 1σ level
around residue Ala58[Rbx] (yellow) and residues Ile44[Ub] and
Val70[Ub] (green).
(C) Interactions between Ub (green) and
MIU (yellow). Hydrogen bonds and salt bridges are indicated by
dashed black lines.
(D) Ub binding residues of the MIU of
Rabex-5 (yellow) and of the UIM of Vps27 (red). Models of the
RZF-MIU:Ub complex and the Vps27-UIM:Ub complex (Swanson et al.,
2003) were superimposed based on residues 5–70 of the Ub
molecules. Side chains involved in interaction between MIU
(yellow)/UIM (red) and Ub are shown in stick representation.
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The above figures are
reprinted
by permission from Cell Press:
Cell
(2006,
124,
1183-1195)
copyright 2006.
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