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PDBsum entry 2fid
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Protein turnover/endocytosis
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PDB id
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2fid
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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 ubiquitin recognition and autoubiquitination by rabex-5.
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Authors
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S.Lee,
Y.C.Tsai,
R.Mattera,
W.J.Smith,
M.S.Kostelansky,
A.M.Weissman,
J.S.Bonifacino,
J.H.Hurley.
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Ref.
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Nat Struct Mol Biol, 2006,
13,
264-271.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
0%.
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Abstract
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Rabex-5 is an exchange factor for Rab5, a master regulator of endosomal
trafficking. Rabex-5 binds monoubiquitin, undergoes covalent ubiquitination and
contains an intrinsic ubiquitin ligase activity, all of which require an
N-terminal A20 zinc finger followed immediately by a helix. The structure of the
N-terminal portion of Rabex-5 bound to ubiquitin at 2.5-A resolution shows that
Rabex-5-ubiquitin interactions occur at two sites. The first site is a new type
of ubiquitin-binding domain, an inverted ubiquitin-interacting motif, which
binds with approximately 29-microM affinity to the canonical Ile44 hydrophobic
patch on ubiquitin. The second is a diaromatic patch on the A20 zinc finger,
which binds with approximately 22-microM affinity to a polar region centered on
Asp58 of ubiquitin. The A20 zinc-finger diaromatic patch mediates
ubiquitin-ligase activity by directly recruiting a ubiquitin-loaded
ubiquitin-conjugating enzyme.
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Figure 1.
Figure 1. Structure of the Rabex-5 A20 ZnF domain and IUIM.
(a) The domain structures of Rabex-5 and the construct used in
this study. Magenta, ZnF domain; green, IUIM; HB, helical
bundle; Vps9, Vps9-homology domain; CC, coiled coil; PR,
proline-rich. (b) Rabex-5 (ribbon) contacts ubiquitin (orange
and blue surfaces) at two sites in the crystal lattice. (c)
Superposition of the four crystallographically independent
molecules of the A20 ZnF domain and IUIM. Green, P6[1] molecule;
pink, magenta and red, the three independent molecules in the
asymmetric unit of the C2 lattice. (d) The zinc-binding site in
the A20 ZnF domain. Orange, sulfurs of cysteine side chains; red
sphere, zinc. (e) Ribbon and stick representation showing
exposed hydrophobic side chains. (f) Surface of the A20 ZnF
domain and IUIM colored by residue type: green, hydrophobic;
red, acidic; blue, basic; white, uncharged polar; yellow,
cysteine.
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Figure 2.
Figure 2. Ubiquitin recognition by Rabex-5. (a) Ubiquitin
(beige ribbon and stick model) bound to Rabex-5 IUIM (green
surface model). (b) Rabex-5 IUIM (green ribbon and sticks) bound
to ubiquitin (orange surface). (c) Ubiquitin (blue ribbon and
sticks) bound to Rabex-5 A20 ZnF domain (magenta surface). (d)
Rabex-5 A20 ZnF domain (magenta ribbon and sticks) bound to
ubiquitin (blue surface). (e) Ubiquitin binds Rabex-5 through
two different nonoverlapping surfaces on ubiquitin. Orange,
surfaces contacting the IUIM; blue, surfaces contacting the A20
ZnF.
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
Nat Struct Mol Biol
(2006,
13,
264-271)
copyright 2006.
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