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PDBsum entry 2o1v
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References listed in PDB file
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Key reference
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Title
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Structures of grp94-Nucleotide complexes reveal mechanistic differences between the hsp90 chaperones.
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Authors
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D.E.Dollins,
J.J.Warren,
R.M.Immormino,
D.T.Gewirth.
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Ref.
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Mol Cell, 2007,
28,
41-56.
[DOI no: ]
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PubMed id
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Abstract
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GRP94, an essential endoplasmic reticulum chaperone, is required for the
conformational maturation of proteins destined for cell-surface display or
export. The extent to which GRP94 and its cytosolic paralog, Hsp90, share a
common mechanism remains controversial. GRP94 has not been shown conclusively to
hydrolyze ATP or bind cochaperones, and both activities, by contrast, result in
conformational changes and N-terminal dimerization in Hsp90 that are critical
for its function. Here, we report the 2.4 A crystal structure of mammalian GRP94
in complex with AMPPNP and ADP. The chaperone is conformationally insensitive to
the identity of the bound nucleotide, adopting a "twisted V"
conformation that precludes N-terminal domain dimerization. We also present
conclusive evidence that GRP94 possesses ATPase activity. Our observations
provide a structural explanation for GRP94's observed rate of ATP hydrolysis and
suggest a model for the role of ATP binding and hydrolysis in the GRP94
chaperone cycle.
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Figure 4.
Figure 4. The C-Terminal Domain of GRP94 Has Additional Dimer
Interactions
(A and B) The C-terminal domain. Helices
comprising the strap residues are shown in gold.
(C) A
potential client-binding surface composed of Met-Met pairs and
hydrophobic residues.
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Figure 5.
Figure 5. ADP- and AMPPNP-Bound GRP94 Have Identical
Conformations
(A) Overlay of the two nucleotide-bound
complexes. The AMPPNP complex is in blue, and the ADP complex is
in cyan. Only one protomer of the GRP94 dimer is shown.
(B)
Stereo view of the bound AMPPNP. SA omit electron density
contoured at 1.3 σ is shown with a 2 Å carve radius. The
density for the nucleotide is shown in green, for the residues
of the N domain in pink, and for the M domain in blue. The
position of Arg448 is indicated, and the distance to the
γ-phosphate of the AMPPNP is shown with a dashed line.
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The above figures are
reprinted
from an Open Access publication published by Cell Press:
Mol Cell
(2007,
28,
41-56)
copyright 2007.
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