PDBsum entry 1qyh

Chaperone

PDB id: 1qyh

Contents

Protein chains

225 a.a.

Ligands

NEC ×2

Waters ×387

Superseded by:

1u2o

PDB id:

1qyh

Name:

Chaperone

Title:

Crystal structure of the n-domain of grp94 lacking the charged domain in complex with neca

Structure:

Endoplasmin. Chain: a, b. Fragment: n-terminal domain delta 40. Synonym: 94 kda glucose-regulated protein, grp94. Engineered: yes

Source:

Canis familiaris. Dog. Gene: tra1. Expressed in: escherichia coli.

Resolution:

2.10Å R-factor: 0.250 R-free: 0.300

Authors:

K.L.Soldano,A.Jivan,C.V.Nicchitta,D.T.Gewirth

Key ref:

K.L.Soldano et al. (2003). Structure of the N-terminal domain of GRP94. Basis for ligand specificity and regulation. J Biol Chem, 278, 48330-48338. PubMed id: 12970348 DOI: 10.1074/jbc.M308661200

Date:

10-Sep-03 Release date: 11-Nov-03

Protein chains

P41148  (ENPL_CANLF) -  Endoplasmin from Canis lupus familiaris

Seq: 804 a.a.

Struc: 225 a.a.*

* PDB and UniProt seqs differ at 8 residue positions (black crosses)

DOI no: 10.1074/jbc.M308661200

J Biol Chem 278:48330-48338 (2003)

PubMed id: 12970348

Structure of the N-terminal domain of GRP94. Basis for ligand specificity and regulation.

K.L.Soldano, A.Jivan, C.V.Nicchitta, D.T.Gewirth.

ABSTRACT

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.

Selected figure(s)

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).

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.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 48330-48338) copyright 2003.

Figures were selected by an automated process.