PDBsum entry 3d2e

Chaperone

PDB id: 3d2e

Contents

Protein chains

629 a.a. *

379 a.a. *

Ligands

ATP ×2

GOL

Metals

_MG ×2

Waters ×428

* Residue conservation analysis

PDB id:

3d2e

Name:

Chaperone

Title:

Crystal structure of a complex of sse1p and hsp70, selenomethionine- labeled crystals

Structure:

Heat shock protein homolog sse1. Chain: a, c. Synonym: chaperone protein msi3. Engineered: yes. Heat shock 70 kda protein 1. Chain: b, d. Synonym: hsp70.1, hsp70-1/hsp70-2. Engineered: yes

Source:

Saccharomyces cerevisiae. Brewer's yeast,lager beer yeast,yeast. Organism_taxid: 4932. Gene: sse1, msi3, ypl106c, lpg3c. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606.

Resolution:

2.35Å R-factor: 0.213 R-free: 0.262

Authors:

S.Polier,A.Bracher

Key ref:

S.Polier et al. (2008). Structural basis for the cooperation of Hsp70 and Hsp110 chaperones in protein folding. Cell, 133, 1068-1079. PubMed id: 18555782 DOI: 10.1016/j.cell.2008.05.022

Date:

08-May-08 Release date: 17-Jun-08

Protein chains

P32589  (HSP7F_YEAST) -  Heat shock protein homolog SSE1 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 693 a.a.

Struc: 629 a.a.

Protein chains

P0DMV8  (HS71A_HUMAN) -  Heat shock 70 kDa protein 1A from Homo sapiens

Seq: 641 a.a.

Struc: 379 a.a.

DOI no: 10.1016/j.cell.2008.05.022

Cell 133:1068-1079 (2008)

PubMed id: 18555782

Structural basis for the cooperation of Hsp70 and Hsp110 chaperones in protein folding.

S.Polier, Z.Dragovic, F.U.Hartl, A.Bracher.

ABSTRACT

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.

Selected figure(s)

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.

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.

The above figures are reprinted by permission from Cell Press: Cell (2008, 133, 1068-1079) copyright 2008.

Figures were selected by the author.