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PDBsum entry 2qwr
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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 of j cochaperone binding and regulation of hsp70.
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Authors
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J.Jiang,
E.G.Maes,
A.B.Taylor,
L.Wang,
A.P.Hinck,
E.M.Lafer,
R.Sousa.
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Ref.
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Mol Cell, 2007,
28,
422-433.
[DOI no: ]
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PubMed id
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Abstract
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The many protein processing reactions of the ATP-hydrolyzing Hsp70s are
regulated by J cochaperones, which contain J domains that stimulate Hsp70 ATPase
activity and accessory domains that present protein substrates to Hsp70s. We
report the structure of a J domain complexed with a J responsive portion of a
mammalian Hsp70. The J domain activates ATPase activity by directing the linker
that connects the Hsp70 nucleotide binding domain (NBD) and substrate binding
domain (SBD) toward a hydrophobic patch on the NBD surface. Binding of the J
domain to Hsp70 displaces the SBD from the NBD, which may allow the SBD
flexibility to capture diverse substrates. Unlike prokaryotic Hsp70, the SBD and
NBD of the mammalian chaperone interact in the ADP state. Thus, although both
nucleotides and J cochaperones modulate Hsp70 NBD:linker and NBD:SBD
interactions, the intrinsic persistence of those interactions differs in
different Hsp70s and this may optimize their activities for different cellular
roles.
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Figure 2.
Figure 2. The NBD_Linker:Auxilin J Domain Complex
(A)
NBD_Linker:auxilin J Domain complex with J domain (cyan) in
ribbon representation and NBD_Linker rendered as a transparent
surface (green; with aa 383–390 in magenta) with the path of
the polypeptide chain shown as a coil and the bound nucleotide
in stick representation.
(B) Model from (A) rotated as
indicated. In yellow on the J domain are regions corresponding
to those mapped by NMR (in the polyoma virus T antigen) to be
involved in interaction with Hsc70 (Garimella et al., 2006).
(C) The region indicated by the box in (B) expanded to
identify residues important for the J domain:Hsc70 interaction.
These are labeled with white lettering on the surface of the
Hsc70, which is colored green, red, and blue for carbon, oxygen,
and nitrogen atoms, respectively, and with black lettering on
the J domain with stick representations of the side chains of
relevant J domain residues colored cyan, red, and blue for
carbon, oxygen, and nitrogen atoms, respectively.
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Figure 4.
Figure 4. J Domain-Induced Changes in Linker Conformation May
Activate ATPase through Interactions with Y371 and I181
(A)
Structures of the J domain (cyan) and Hsc70 residues 371–389,
181, and 187 with the linker in the “Out” conformation.
Hsc70 linker residues 383–389 and 371–382+181+187 are in
magenta and green, respectively. The ED around the illustrated
Hsc70 residues is contoured at 0.5 σ.
(B) As in (A), but
with the linker in the “In” conformation and extending to
residue 390; average B factors for linker residues 383–389
(“Out”) or 383–390 (“In”) are 55 and 56, respectively,
whereas the average B factor for residues 3–382 of the NBD is
28.
(C) Effects of J domain on the ATPase rates of WT and
mutant Hsc70ΔC enzymes. Experimental conditions as in Figure 1,
but with Hsc70ΔC and J domain (+J) at 10 and 25 μM,
respectively. Error bars are ± SEM for n = 3.
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The above figures are
reprinted
from an Open Access publication published by Cell Press:
Mol Cell
(2007,
28,
422-433)
copyright 2007.
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