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PDBsum entry 1gnu
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* Residue conservation analysis
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DOI no:
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J Biol Chem
277:5556-5561
(2002)
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PubMed id:
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The X-ray crystal structure and putative ligand-derived peptide binding properties of gamma-aminobutyric acid receptor type A receptor-associated protein.
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D.Knight,
R.Harris,
M.S.McAlister,
J.P.Phelan,
S.Geddes,
S.J.Moss,
P.C.Driscoll,
N.H.Keep.
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ABSTRACT
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The gamma-aminobutyric acid receptor type A (GABA(A)) receptor-associated
protein (GABARAP) has been reported to mediate the interaction between the
GABA(A) receptor and microtubules. We present the three-dimensional structure of
GABARAP obtained by x-ray diffraction at 1.75 A resolution. The structure was
determined by molecular replacement using the structure of the homologous
protein GATE-16. NMR spectroscopy of isotope-labeled GABARAP showed the
structure in solution to be compatible with the overall fold but showed evidence
of conformation heterogeneity that is not apparent in the crystal structure. We
assessed the binding of GABARAP to peptides derived from reported binding
partner proteins, including the M3-M4 loop of the gamma2 subunit of the GABA(A)
receptor and the acidic carboxyl-terminal tails of human alpha- and
beta-tubulin. There is a small area of concentrated positive charge on one
surface of GABARAP, which we found interacts weakly with all peptides tested,
but we found no evidence for specific binding to the proposed physiological
target peptides. These results are compatible with a more general role in
membrane targeting and transportation for the GABARAP family of proteins.
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Selected figure(s)
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Figure 1.
Fig. 1. a, stereo representation of the superposition of
the GABARAP and GATE-16 main chains. b, cartoon diagram of the
GABARAP three-dimensional backbone structure. Region 1-35 is in
green, region 35-68 is in red, and region 68-117 is in blue.
Therefore, the baits used in the two hybrids are the 35-117
region (colored in red and blue) and the 1-68 region (colored in
green and red). c, backbone trace of GABARAP in the same
orientation as b, showing residues discussed in the text.
Conserved residues are shown in red for acidic residues, blue
for basic residues, magenta for polar residues, green for
residues involved in turns, and black for hydrophobic core
residues. The nonconserved Phe^3 is shown in light gray, and
water molecules involved in the region of the salt bridges are
shown in cyan. This figure was prepared with MOLSCRIPT (32) and
RASTER3D (33).
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Figure 4.
Fig. 4. Backbone traces of GABARAP structure (cyan)
superposed by yellow spheres indicating NH groups for residues
that experience chemical shift perturbations upon addition of
candidate peptide ligands I  V in A E,
respectively. Three different sphere sizes are used to indicate
the different classes of perturbation described in Table II:
large sphere, >1 linewidth; medium sphere, approximately 1
linewidth; and small sphere, <1 linewidth. F, space-filled
representation of the GABARAP structure colored according to the
surface electrostatic potential computed with the program GRASP
(25), with orientation identical to that in A E.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2002,
277,
5556-5561)
copyright 2002.
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Figures were
selected
by the author.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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J.Alam,
D.Deharo,
K.M.Redding,
R.N.Re,
and
J.L.Cook
(2010).
C-terminal processing of GABARAP is not required for trafficking of the angiotensin II type 1A receptor.
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Regul Pept,
159,
78-86.
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P.Ma,
J.Mohrlüder,
M.Schwarten,
M.Stoldt,
S.K.Singh,
R.Hartmann,
V.Pacheco,
and
D.Willbold
(2010).
Preparation of a functional GABARAP-lipid conjugate in nanodiscs and its investigation by solution NMR spectroscopy.
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Chembiochem,
11,
1967-1970.
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V.Pacheco,
P.Ma,
Y.Thielmann,
R.Hartmann,
O.H.Weiergräber,
J.Mohrlüder,
and
D.Willbold
(2010).
Assessment of GABARAP self-association by its diffusion properties.
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J Biomol NMR,
48,
49-58.
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J.A.Doebbler,
and
R.B.Von Dreele
(2009).
Application of molecular replacement to protein powder data from image plates.
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Acta Crystallogr D Biol Crystallogr,
65,
348-355.
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J.Mohrlüder,
M.Schwarten,
and
D.Willbold
(2009).
Structure and potential function of gamma-aminobutyrate type A receptor-associated protein.
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FEBS J,
276,
4989-5005.
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Y.Chen,
C.Chen,
E.Kotsikorou,
D.L.Lynch,
P.H.Reggio,
and
L.Y.Liu-Chen
(2009).
GEC1-kappa opioid receptor binding involves hydrophobic interactions: GEC1 has chaperone-like effect.
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J Biol Chem,
284,
1673-1685.
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L.Sanchez-Pulido,
D.Devos,
Z.R.Sung,
and
M.Calonje
(2008).
RAWUL: a new ubiquitin-like domain in PRC1 ring finger proteins that unveils putative plant and worm PRC1 orthologs.
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BMC Genomics,
9,
308.
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N.N.Noda,
H.Kumeta,
H.Nakatogawa,
K.Satoo,
W.Adachi,
J.Ishii,
Y.Fujioka,
Y.Ohsumi,
and
F.Inagaki
(2008).
Structural basis of target recognition by Atg8/LC3 during selective autophagy.
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Genes Cells,
13,
1211-1218.
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PDB codes:
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Y.Thielmann,
J.Mohrlüder,
B.W.Koenig,
T.Stangler,
R.Hartmann,
K.Becker,
H.D.Höltje,
and
D.Willbold
(2008).
An indole-binding site is a major determinant of the ligand specificity of the GABA type A receptor-associated protein GABARAP.
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Chembiochem,
9,
1767-1775.
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J.Mohrlüder,
T.Stangler,
Y.Hoffmann,
K.Wiesehan,
A.Mataruga,
and
D.Willbold
(2007).
Identification of calreticulin as a ligand of GABARAP by phage display screening of a peptide library.
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FEBS J,
274,
5543-5555.
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Z.W.Chen,
and
R.W.Olsen
(2007).
GABAA receptor associated proteins: a key factor regulating GABAA receptor function.
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J Neurochem,
100,
279-294.
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N.Amar,
G.Lustig,
Y.Ichimura,
Y.Ohsumi,
and
Z.Elazar
(2006).
Two newly identified sites in the ubiquitin-like protein Atg8 are essential for autophagy.
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EMBO Rep,
7,
635-642.
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B.Lüscher,
and
C.A.Keller
(2004).
Regulation of GABAA receptor trafficking, channel activity, and functional plasticity of inhibitory synapses.
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Pharmacol Ther,
102,
195-221.
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I.Dreveny,
H.Kondo,
K.Uchiyama,
A.Shaw,
X.Zhang,
and
P.S.Freemont
(2004).
Structural basis of the interaction between the AAA ATPase p97/VCP and its adaptor protein p47.
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EMBO J,
23,
1030-1039.
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PDB code:
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K.Sugawara,
N.N.Suzuki,
Y.Fujioka,
N.Mizushima,
Y.Ohsumi,
and
F.Inagaki
(2004).
The crystal structure of microtubule-associated protein light chain 3, a mammalian homologue of Saccharomyces cerevisiae Atg8.
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Genes Cells,
9,
611-618.
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PDB code:
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M.Kneussel
(2002).
Dynamic regulation of GABA(A) receptors at synaptic sites.
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Brain Res Brain Res Rev,
39,
74-83.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
