PDBsum entry 2qwq

Chaperone

PDB id: 2qwq

Contents

Protein chains

383 a.a. *

92 a.a. *

Ligands

PO4

ADP

ACY

GOL ×2

Waters ×105

* Residue conservation analysis

PDB id:

2qwq

Name:

Chaperone

Title:

Crystal structure of disulfide-bond-crosslinked complex of bovine hsc70 (1-394aa)r171c and bovine auxilin (810-910aa)d876c in the amppnp hydrolyzed form

Structure:

Heat shock cognate 71 kda protein. Chain: a. Synonym: heat shock 70 kda protein 8. Engineered: yes. Mutation: yes. Putative tyrosine-protein phosphatase auxilin. Chain: b. Synonym: dnaj homolog subfamily c member 6. Engineered: yes.

Source:

Bos taurus. Cattle. Organism_taxid: 9913. Gene: hspa8, hsc70. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: dnajc6. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.21Å R-factor: 0.243 R-free: 0.295

Authors:

J.Jiang,E.G.Maes,L.Wang,A.B.Taylor,A.P.Hinck,E.M.Lafer,R.Sousa

Key ref:

J.Jiang et al. (2007). Structural basis of J cochaperone binding and regulation of Hsp70. Mol Cell, 28, 422-433. PubMed id: 17996706 DOI: 10.1016/j.molcel.2007.08.022

Date:

10-Aug-07 Release date: 18-Dec-07

Protein chain

P19120  (HSP7C_BOVIN) -  Heat shock cognate 71 kDa protein from Bos taurus

Seq: 650 a.a.

Struc: 383 a.a.*

Protein chain

Q27974  (AUXI_BOVIN) -  Auxilin from Bos taurus

Seq: 910 a.a.

Struc: 92 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: Chain A: E.C.3.6.4.10 - non-chaperonin molecular chaperone ATPase.
• Reaction: ATP + H2O = ADP + phosphate + H⁺

ATP + H2O = ADP + phosphate (Bound ligand (Het Group name = PO4) corresponds exactly) + H(+)

• Enzyme class 2: Chain B: E.C.3.1.3.- - ?????

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.molcel.2007.08.022

Mol Cell 28:422-433 (2007)

PubMed id: 17996706

Structural basis of J cochaperone binding and regulation of Hsp70.

J.Jiang, E.G.Maes, A.B.Taylor, L.Wang, A.P.Hinck, E.M.Lafer, R.Sousa.

ABSTRACT

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.

Selected figure(s)

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.

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.

The above figures are reprinted from an Open Access publication published by Cell Press: Mol Cell (2007, 28, 422-433) copyright 2007.

Figures were selected by an automated process.