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PDBsum entry 3d2e
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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 the cooperation of hsp70 and hsp110 chaperones in protein folding.
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Authors
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S.Polier,
Z.Dragovic,
F.U.Hartl,
A.Bracher.
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Ref.
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Cell, 2008,
133,
1068-1079.
[DOI no: ]
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PubMed id
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Abstract
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Protein folding by Hsp70 is tightly controlled by cochaperones, including
J-domain proteins that trigger ATP hydrolysis and nucleotide exchange factors
(NEFs) that remove ADP from Hsp70. Here we present the crystal structure of the
yeast NEF Sse1p (Hsp110) in complex with the nucleotide-binding domain (NBD) of
Hsp70. Hsp110 proteins are homologous to Hsp70s and consist of an NBD, a beta
sandwich domain, and a three helix bundle domain (3HBD). In the complex, the NBD
of Sse1p is ATP bound, and together with the 3HBD it embraces the NBD of Hsp70,
inducing opening and the release of bound ADP from Hsp70. Mutations that abolish
NEF activity are lethal, thus defining nucleotide exchange on Hsp70 as an
essential function of Sse1p. Our data suggest that Sse1p does not employ the
nucleotide-dependent allostery and peptide-binding mode of canonical Hsp70s, and
that direct interactions of substrate with Sse1p may support Hsp70-assisted
protein folding in a cooperative process.
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Figure 1.
Figure 1. Crystal Structure of the Sse1p·ATP-Hsp70N
Complex
(A) Frontal view of the complex. Sse1p is shown in
ribbon representation with the NBD colored in dark blue, the
linker segment in yellow (in the background), and the β
sandwich and 3HBD in brown and green, respectively. The NBD of
human Hsp70, Hsp70N, is shown in surface representation in dark
red. The subdomain structure of Hsp70N is indicated.
(B)
Bottom view of the complex in surface representation using the
same coloring scheme as in (A).
(C) Cut-away views onto the
Hsp70N-Sse1p interface. The position of the interaction partner
is indicated by its outline. Interacting atoms are colored in
orange. Water molecules connecting the binding partners via
hydrogen bonds are indicated as beige spheres. ATP is shown in
ball-and-stick representation. The subdomain structures of the
NBDs are indicated.
(D) Surface conservation of the Sse1p
interface. The color gradient from red to cyan indicates
decreasing conservation. The corresponding representation for
the Hsp70N binding face can be found in Figure S2.
(E)
Superposition of the Hsp70N·ADP complex (light blue) with
Hsp70N from the Sse1p·ATP-Hsp70N structure (red). The
position of Sse1p is indicated by an outline. The orientation of
the structure is the same as in (C) and (D). Subdomain IIb of
the Hsp70N·ADP complex would clash with subdomain IIb in
Sse1p.
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Figure 2.
Figure 2. Key Interactions at the Sse1p·ATP-Hsp70N
Interface
(A) Closeup view of the contacts between
subdomain IIb of Hsp70N and the 3HBD of Sse1p.
(B) Contact
interface in the vicinity of the Sse1p-bound ATP molecule.
(C) Region of close surface complementarity between Sse1p and
subdomain Ia of Hsp70N.
In (A)–(C), both protein
backbones are shown in ribbon representation with the exception
of regions involved in intermolecular contacts. These regions
and the corresponding side chains are depicted in stick
representation. Sse1p is enveloped in a transparent molecular
surface to highlight the close surface complementarity. The
color coding for molecular surfaces, backbone, and carbon atoms
is identical to that in Figure 1A. Sse1p-bound ATP is
represented in a ball-and-stick model with carbon atoms colored
in yellow. Nitrogen and oxygen atoms are indicated in blue and
red, respectively. Ordered water molecules bridging the binding
partners are shown as beige spheres. Hydrogen bonds are
represented as dashed lines. Key interacting residues are
indicated. In all panels, unrelated obstructing features in the
foreground were omitted for clarity.
(D) Alignment of
Hsp110, Hsp70, and DnaK amino acid sequences at the contact
region between the 3HBD of Sse1p and subdomain IIb of Hsp70N.
Contacting residues are indicated below the sequence with the
interacting domain indicated by the color scheme used in Figure
1A. Notable differences in the consensus sequences for Hsp110s
and canonical Hsp70s are boxed. An unabridged version of the
alignment is shown in Figure S5.
(E) Sequence alignment of
residues involved in the contact close to the nucleotide-binding
pocket of Sse1p.
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The above figures are
reprinted
by permission from Cell Press:
Cell
(2008,
133,
1068-1079)
copyright 2008.
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