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PDBsum entry 2qwp

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protein ligands metals Protein-protein interface(s) links
Chaperone PDB id
2qwp
Jmol
Contents
Protein chains
386 a.a. *
92 a.a. *
Ligands
ADP
PO4
ACY
GOL ×2
Metals
_NA ×2
_MG
Waters ×290
* Residue conservation analysis
PDB id:
2qwp
Name: Chaperone
Title: Crystal structure of disulfide-bond-crosslinked complex of b hsc70 (1-394aa)r171c and bovine auxilin (810-910aa)d876c in adp Pi form #2
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:
1.75Å     R-factor:   0.205     R-free:   0.243
Authors: J.Jiang,E.G.Maes,L.Wang,A.B.Taylor,A.P.Hinck,E.M.Lafer,R.Sou
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    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P19120  (HSP7C_BOVIN) -  Heat shock cognate 71 kDa protein
Seq:
Struc:
 
Seq:
Struc:
650 a.a.
386 a.a.*
Protein chain
Pfam   ArchSchema ?
Q27974  (AUXI_BOVIN) -  Putative tyrosine-protein phosphatase auxilin
Seq:
Struc:
 
Seq:
Struc:
910 a.a.
92 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chain B: E.C.3.1.3.48  - Protein-tyrosine-phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Protein tyrosine phosphate + H2O = protein tyrosine + phosphate
Protein tyrosine phosphate
+ H(2)O
= protein tyrosine
+
phosphate
Bound ligand (Het Group name = PO4)
corresponds exactly
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.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21482798 A.Zhuravleva, and L.M.Gierasch (2011).
Allosteric signal transmission in the nucleotide-binding domain of 70-kDa heat shock protein (Hsp70) molecular chaperones.
  Proc Natl Acad Sci U S A, 108, 6987-6992.  
21338918 L.Chang, Y.Miyata, P.M.Ung, E.B.Bertelsen, T.J.McQuade, H.A.Carlson, E.R.Zuiderweg, and J.E.Gestwicki (2011).
Chemical screens against a reconstituted multiprotein complex: myricetin blocks DnaJ regulation of DnaK through an allosteric mechanism.
  Chem Biol, 18, 210-221.  
21329881 M.Hagiwara, K.Maegawa, M.Suzuki, R.Ushioda, K.Araki, Y.Matsumoto, J.Hoseki, K.Nagata, and K.Inaba (2011).
Structural basis of an ERAD pathway mediated by the ER-resident protein disulfide reductase ERdj5.
  Mol Cell, 41, 432-444.
PDB codes: 3apo 3apq 3aps
20562448 A.Takano, N.Suetsugu, M.Wada, and D.Kohda (2010).
Crystallographic and functional analyses of J-domain of JAC1 essential for chloroplast photorelocation movement in Arabidopsis thaliana.
  Plant Cell Physiol, 51, 1372-1376.
PDB code: 3ag7
19822657 C.Sahi, T.Lee, M.Inada, J.A.Pleiss, and E.A.Craig (2010).
Cwc23, an essential J protein critical for pre-mRNA splicing with a dispensable J domain.
  Mol Cell Biol, 30, 33-42.  
20651708 H.H.Kampinga, and E.A.Craig (2010).
The HSP70 chaperone machinery: J proteins as drivers of functional specificity.
  Nat Rev Mol Cell Biol, 11, 579-592.  
20453930 J.C.Young (2010).
Mechanisms of the Hsp70 chaperone system.
  Biochem Cell Biol, 88, 291-300.  
19923195 J.Hoseki, R.Ushioda, and K.Nagata (2010).
Mechanism and components of endoplasmic reticulum-associated degradation.
  J Biochem, 147, 19-25.  
20385092 K.Mapa, M.Sikor, V.Kudryavtsev, K.Waegemann, S.Kalinin, C.A.Seidel, W.Neupert, D.C.Lamb, and D.Mokranjac (2010).
The conformational dynamics of the mitochondrial Hsp70 chaperone.
  Mol Cell, 38, 89.  
20007714 M.Blamowska, M.Sichting, K.Mapa, D.Mokranjac, W.Neupert, and K.Hell (2010).
ATPase domain and interdomain linker play a key role in aggregation of mitochondrial Hsp70 chaperone Ssc1.
  J Biol Chem, 285, 4423-4431.  
20179333 M.Shida, A.Arakawa, R.Ishii, S.Kishishita, T.Takagi, M.Kukimoto-Niino, S.Sugano, A.Tanaka, M.Shirouzu, and S.Yokoyama (2010).
Direct inter-subdomain interactions switch between the closed and open forms of the Hsp70 nucleotide-binding domain in the nucleotide-free state.
  Acta Crystallogr D Biol Crystallogr, 66, 223-232.
PDB codes: 2e88 2e8a
20865007 R.G.Smock, O.Rivoire, W.P.Russ, J.F.Swain, S.Leibler, R.Ranganathan, and L.M.Gierasch (2010).
An interdomain sector mediating allostery in Hsp70 molecular chaperones.
  Mol Syst Biol, 6, 414.  
  20862304 Y.Liu, L.M.Gierasch, and I.Bahar (2010).
Role of Hsp70 ATPase domain intrinsic dynamics and sequence evolution in enabling its functional interactions with NEFs.
  PLoS Comput Biol, 6, 0.  
20033059 Y.Xing, T.Böcking, M.Wolf, N.Grigorieff, T.Kirchhausen, and S.C.Harrison (2010).
Structure of clathrin coat with bound Hsc70 and auxilin: mechanism of Hsc70-facilitated disassembly.
  EMBO J, 29, 655-665.  
19036727 D.Becker, M.Krayl, A.Strub, Y.Li, M.P.Mayer, and W.Voos (2009).
Impaired Interdomain Communication in Mitochondrial Hsp70 Results in the Loss of Inward-directed Translocation Force.
  J Biol Chem, 284, 2934-2946.  
19519514 D.Sharma, and D.C.Masison (2009).
Hsp70 structure, function, regulation and influence on yeast prions.
  Protein Pept Lett, 16, 571-581.  
19883127 H.J.Woo, J.Jiang, E.M.Lafer, and R.Sousa (2009).
ATP-induced conformational changes in Hsp70: molecular dynamics and experimental validation of an in silico predicted conformation.
  Biochemistry, 48, 11470-11477.  
19549854 P.Kota, D.W.Summers, H.Y.Ren, D.M.Cyr, and N.V.Dokholyan (2009).
Identification of a consensus motif in substrates bound by a Type I Hsp40.
  Proc Natl Acad Sci U S A, 106, 11073-11078.  
18550409 J.P.Schuermann, J.Jiang, J.Cuellar, O.Llorca, L.Wang, L.E.Gimenez, S.Jin, A.B.Taylor, B.Demeler, K.A.Morano, P.J.Hart, J.M.Valpuesta, E.M.Lafer, and R.Sousa (2008).
Structure of the Hsp110:Hsc70 nucleotide exchange machine.
  Mol Cell, 31, 232-243.
PDB code: 3c7n
18923430 K.Petrova, S.Oyadomari, L.M.Hendershot, and D.Ron (2008).
Regulated association of misfolded endoplasmic reticulum lumenal proteins with P58/DNAJc3.
  EMBO J, 27, 2862-2872.  
18706386 P.G.Needham, and D.C.Masison (2008).
Prion-impairing mutations in Hsp70 chaperone Ssa1: effects on ATPase and chaperone activities.
  Arch Biochem Biophys, 478, 167-174.  
18684711 S.Tzankov, M.J.Wong, K.Shi, C.Nassif, and J.C.Young (2008).
Functional Divergence between Co-chaperones of Hsc70.
  J Biol Chem, 283, 27100-27109.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.