PDBsum entry 1yt2

Chaperone

PDB id: 1yt2

Contents

Protein chain

225 a.a. *

Ligands

PG4 ×4

Waters ×16

* Residue conservation analysis

PDB id:

1yt2

Name:

Chaperone

Title:

Crystal structure of the unliganded form of grp94, the er hsp90: basis for nucleotide-induced conformational change, grp94n apo crystal

Structure:

Endoplasmin. Chain: a. Fragment: n-terminal domain of grp94 residues (69-337). Synonym: 94 kda glucose-regulated protein, grp94. Engineered: yes

Source:

Canis lupus familiaris. Dog. Organism_taxid: 9615. Strain: familiaris. Gene: tra1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

3.25Å R-factor: 0.252 R-free: 0.293

Authors:

D.E.Dollins,R.M.Immormino,D.T.Gewirth

Key ref:

D.E.Dollins et al. (2005). Structure of unliganded GRP94, the endoplasmic reticulum Hsp90. Basis for nucleotide-induced conformational change. J Biol Chem, 280, 30438-30447. PubMed id: 15951571 DOI: 10.1074/jbc.M503761200

Date:

09-Feb-05 Release date: 14-Jun-05

Protein chain

P41148  (ENPL_CANLF) -  Endoplasmin from Canis lupus familiaris

Seq: 804 a.a.

Struc: 225 a.a.*

* PDB and UniProt seqs differ at 9 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.6.4.- - ?????

DOI no: 10.1074/jbc.M503761200

J Biol Chem 280:30438-30447 (2005)

PubMed id: 15951571

Structure of unliganded GRP94, the endoplasmic reticulum Hsp90. Basis for nucleotide-induced conformational change.

D.E.Dollins, R.M.Immormino, D.T.Gewirth.

ABSTRACT

GRP94, the endoplasmic reticulum paralog of Hsp90, is regulated by adenosine nucleotides that bind to its N-terminal regulatory domain. Because of its weak affinity for nucleotides, the functionally relevant transition in GRP94 is likely to be between the unliganded and nucleotide-bound states. We have determined the structure of the unliganded GRP94 N-domain. The helix 1-4-5 subdomain of the unliganded protein adopts the closed conformation seen in the structure of the protein in complex with inhibitors. This conformation is distinct from the open conformation of the subdomain seen when the protein is bound to ATP or ADP. ADP soaked into crystals of the unliganded protein reveals an intermediate conformation midway between the open and closed states and demonstrates that in GRP94 the conversion between the open and closed states is driven by ligand binding. The direction of the observed movement in GRP94 shows that nucleotides act to open the subdomain elements rather than close them, which is contrary to the motion proposed for Hsp90. These observations support a model where ATP binding dictates the conformation of the N-domain and regulates its ability to form quaternary structural interactions.

Selected figure(s)

Figure 6.
FIG. 6. Solvent arrangements in the ligand binding cavity of unliganded GRP94. A, stereo drawing of the residues lining the cavity and the solvent molecules within the cavity. Hydrogen bonds are shown as dashed lines. Water molecules are shown as spheres, and those that are common to all GRP94-ligand complexes are colored purple. Orange-colored waters are conserved in the GRP94 closed conformation but are displaced by nucleotides and the large inhibitor geldanamycin. PEG, polyethylene glycol. B, schematic diagram of the same interactions shown in panel A. Water molecules are colored as in panel A. Hydrogen bonds are shown as green dashed lines. NE, nuclear extract.

Figure 7.
FIG. 7. Model for GRP94 conformational changes in response to ligand. N, middle, and C domains are designated by N, M, and C, respectively. A stands for ATP, and R stands for radicicol. Rdc and Gdm denote radicicol and geldanamycin, respectively. The charged linker domain is disordered in all structure determinations and is represented by a dashed line. The closed N-domain conformation in the unliganded and inhibitor-bound states is indicated by the position of helix 1 and the strand 1/6 interaction. The open N-domain conformation shown in the nucleotide-bound state is indicated by the loss of the strand 1/6 interaction and the helix 1-mediated dimerization interactions.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 30438-30447) copyright 2005.

Figures were selected by an automated process.