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PDBsum entry 2k8c
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Protein binding
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PDB id
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2k8c
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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 by a novel domain from human phospholipase a2-Activating protein.
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Authors
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Q.S.Fu,
C.J.Zhou,
H.C.Gao,
Y.J.Jiang,
Z.R.Zhou,
J.Hong,
W.M.Yao,
A.X.Song,
D.H.Lin,
H.Y.Hu.
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Ref.
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J Biol Chem, 2009,
284,
19043-19052.
[DOI no: ]
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PubMed id
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Abstract
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Ubiquitin (Ub) is an essential modifier conserved in all eukaryotes from yeast
to human. Phospholipase A(2)-activating protein (PLAA), a mammalian homolog of
yeast DOA1/UFD3, has been proposed to be able to bind with Ub, which plays
important roles in endoplasmic reticulum-associated degradation, vesicle
formation, and DNA damage response. We have identified a core domain from the
PLAA family ubiquitin-binding region of human PLAA (residues 386-465, namely
PFUC) that can bind Ub and elucidated its solution structure and Ub-binding mode
by NMR approaches. The PFUC domain possesses equal population of two conformers
in solution by cis/trans-isomerization, whereas the two isomers exhibit almost
equivalent Ub binding abilities. This domain structure takes a novel fold
consisting of four beta-strands and two alpha-helices, and the Ub-binding site
on PFUC locates in the surface of alpha2-helix, which is to some extent
analogous to those of UBA, CUE, and UIM domains. This study provides structural
basis and biochemical information for Ub recognition of the novel PFU domain
from a PLAA family protein that may connect ubiquitination and degradation in
endoplasmic reticulum-associated degradation.
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Figure 4.
Solution structure of the PFUC domain. A, backbone
superposition of 15 lowest-energy structures in cis (left panel)
and trans (right panel) isomers. B, ribbon representation of the
structures for cis (left panel) and trans (right panel) isomers.
N and C indicate the N and C termini of PFUC, respectively. C,
comparison of the cis and trans isomers in the loop between β3
and β4 where Pro^77 resides. The Gly^76–Pro^77 prolyl bonds
in both cis- and trans-isomers are fit together and the side
chain positions of Gly^76 and Pro^77 are shown in red (cis) and
blue (trans).
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Figure 5.
HADDOCK-derived model for the PFUC-Ub complex. A, backbone
superposition of 10 refined cis-PFUC-Ub complex structures. The
average energy for the cluster is −6349 ± 59
kcal·mol^−1 for the cis-PFUC-Ub complex and that is
−6377 ± 81 kcal·mol^−1 for trans-PFUC-Ub. The
root mean square deviation of all backbone atoms in the
interfaces is 1.2 ± 0.8 Å for cis-PFUC-Ub and 1.1
± 0.9 Å for trans-PFUC-Ub. B, close-up view of the
interfaces showing the side chains of key interacting residues.
The stick representations are in red for the side chains from Ub
and in blue for those from PFUC.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2009,
284,
19043-19052)
copyright 2009.
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