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PDBsum entry 1qyh
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References listed in PDB file
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Key reference
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Title
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Structure of the n-Terminal domain of grp94. Basis for ligand specificity and regulation.
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Authors
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K.L.Soldano,
A.Jivan,
C.V.Nicchitta,
D.T.Gewirth.
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Ref.
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J Biol Chem, 2003,
278,
48330-48338.
[DOI no: ]
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PubMed id
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Abstract
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GRP94, the endoplasmic reticulum (ER) paralog of the chaperone Hsp90, plays an
essential role in the structural maturation or secretion of a subset of proteins
destined for transport to the cell surface, such as the Toll-like receptors 2
and 4, and IgG, respectively. GRP94 differs from cytoplasmic Hsp90 by exhibiting
very weak ATP binding and hydrolysis activity. GRP94 also binds selectively to a
series of substituted adenosine analogs. The high resolution crystal structures
at 1.75-2.1 A of the N-terminal and adjacent charged domains of GRP94 in complex
with N-ethylcarboxamidoadenosine, radicicol, and 2-chlorodideoxyadenosine
reveals a structural mechanism for ligand discrimination among hsp90 family
members. The structures also identify a putative subdomain that may act as a
ligand-responsive switch. The residues of the charged region fold into a
disordered loop whose termini are ordered and continue the twisted beta sheet
that forms the structural core of the N-domain. This continuation of the beta
sheet past the charged domain suggests a structural basis for the association of
the N-terminal and middle domains of the full-length chaperone.
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Figure 2.
FIG. 2. Interactions between NECA and GRP94. A, schematic
drawing showing the interactions. Hydrogen bonds are shown as
dashed lines, and van der Waals contacts are represented by
complementary double semi-circles. Red circles are water
molecules. Amino acid side chains are represented by ovals, and
backbone atoms are shown as squares. B, stereo view of the
GRP94·NECA interaction. Selected van der Waals surfaces
are depicted by dots, hydrogen bonds are depicted by dashed
lines, and water molecules are shown as green spheres. Oxygen
atoms are colored red, nitrogen blue, and carbon black. C,
stereo view of the binding of ADP in yeast Hsp90. The
coordinates were taken from PDB code 1AMW [PDB]
(15). B and C were prepared with Ribbons (47).
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Figure 4.
FIG. 4. Strand 9 of GRP94 replaces strand 8 of the yeast
Hsp90 dimer. A, yeast Hsp90 dimer (PDB code 1AMW [PDB]
); B, GRP94 N-domain shown in the same orientation as in panel
A. Strand 9 is colored red. The disordered charged domain is
indicated by a dashed line. C, the GRP94 strand8/strand9
interface. The van der Waals radii are shown as a dot surface.
Strand 8 is in blue with red dots, and strand 9 is in red with
blue dots.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2003,
278,
48330-48338)
copyright 2003.
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