PDBsum entry 3c7n

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protein ligands metals Protein-protein interface(s) links
Chaperone/chaperone PDB id
Protein chains
649 a.a. *
540 a.a. *
SO4 ×4
_MG ×2
_CL ×3
* Residue conservation analysis
PDB id:
Name: Chaperone/chaperone
Title: Structure of the hsp110:hsc70 nucleotide exchange complex
Structure: Heat shock protein homolog sse1. Chain: a. Fragment: residues 1-666. Synonym: chaperone protein msi3. Engineered: yes. Heat shock cognate. Chain: b. Fragment: residues 1-554. Synonym: heat shock 70 kda protein 8.
Source: Saccharomyces cerevisiae. Baker's yeast. Gene: sse1, msi3. Expressed in: escherichia coli. Bos taurus. Bovine. Gene: hspa8, hsc70.
3.12Å     R-factor:   0.227     R-free:   0.283
Authors: J.P.Schuermann,J.Jiang,P.J.Hart,R.Sousa
Key ref:
J.P.Schuermann et al. (2008). Structure of the Hsp110:Hsc70 nucleotide exchange machine. Mol Cell, 31, 232-243. PubMed id: 18550409 DOI: 10.1016/j.molcel.2008.05.006
07-Feb-08     Release date:   27-May-08    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P32589  (HSP7F_YEAST) -  Heat shock protein homolog SSE1
693 a.a.
649 a.a.
Protein chain
Pfam   ArchSchema ?
P19120  (HSP7C_BOVIN) -  Heat shock cognate 71 kDa protein
650 a.a.
540 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   2 terms 
  Biological process     regulation of catalytic activity   3 terms 
  Biochemical function     nucleotide binding     6 terms  


DOI no: 10.1016/j.molcel.2008.05.006 Mol Cell 31:232-243 (2008)
PubMed id: 18550409  
Structure of the Hsp110:Hsc70 nucleotide exchange machine.
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, R.Sousa.
Hsp70s mediate protein folding, translocation, and macromolecular complex remodeling reactions. Their activities are regulated by proteins that exchange ADP for ATP from the nucleotide-binding domain (NBD) of the Hsp70. These nucleotide exchange factors (NEFs) include the Hsp110s, which are themselves members of the Hsp70 family. We report the structure of an Hsp110:Hsc70 nucleotide exchange complex. The complex is characterized by extensive protein:protein interactions and symmetric bridging interactions between the nucleotides bound in each partner protein's NBD. An electropositive pore allows nucleotides to enter and exit the complex. The role of nucleotides in complex formation and dissociation, and the effects of the protein:protein interactions on nucleotide exchange, can be understood in terms of the coupled effects of the nucleotides and protein:protein interactions on the open-closed isomerization of the NBDs. The symmetrical interactions in the complex may model other Hsp70 family heterodimers in which two Hsp70s reciprocally act as NEFs.
  Selected figure(s)  
Figure 2.
Figure 2. Ribbon Models of the Hsp110:Hsc70 Nucleotide Exchange Complex
Hsc70 is colored in blue tones, and Hsp110 is colored in autumn tones (red, orange, yellow, brown). NBDs of Hsp110 and Hsc70 are colored yellow and light cyan, respectively. The interdomain linkers of Hsp110 and Hsc70 are red and blue, respectively. The Hsc70 SBD is dark cyan, and the Hsp110 SBDβ and SBDα are orange and brown, respectively. Subdomains IA–IIB of the NBDs are labeled in (A) and (D), and individual domains are labeled in (B); different views of the complex are related by the indicated rotations.
Figure 4.
Figure 4. Conformation and Oligomeric State of the Hsp110:Hsc70 Complex in Solution
(A)–(G) and (I) show different views of the 3D reconstruction of the Hsp110:Hsc70 complex, while (H) and (J) show reconstructions of an Hsp110:Hsc70 NBD complex. (E)–(G) and (H) also show a ribbon model of the Hsp110:Hsc70 crystal complex (110 NBD: yellow; 110 SBDβ: orange; 110 SBDα: gray; 70 NBD: light cyan; 70 SBD: green) fit into the EM envelope. The model fits very well with the exception of the acidic insertion loop and the Hsc70 SBD. An alternative position for the Hsc70 SBD (red) suggested in (I) and (J) fits very well into the density that is missing in the complex in which the SBD is deleted (arrows in [G] and [H]).
(K) Genetic algorithm Monte Carlo fit of the sedimentation data for the Hsp110:Hsc70 complex. Relative concentrations are shown as a color gradient (white = 0 μM, black = 16 μM). The predominant species (black center) corresponds to the dimer, while the minor species at vert, similar 72 kDa corresponds to free Hsc70ΔC and Hsp110.
  The above figures are reprinted by permission from Cell Press: Mol Cell (2008, 31, 232-243) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20694844 A.Finka, R.U.Mattoo, and P.Goloubinoff (2011).
Meta-analysis of heat- and chemically upregulated chaperone genes in plant and human cells.
  Cell Stress Chaperones, 16, 15-31.  
21482805 A.Rothnie, A.R.Clarke, P.Kuzmic, A.Cameron, and C.J.Smith (2011).
A sequential mechanism for clathrin cage disassembly by 70-kDa heat-shock cognate protein (Hsc70) and auxilin.
  Proc Natl Acad Sci U S A, 108, 6927-6932.  
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.  
  21418353 I.Jungkunz, K.Link, F.Vogel, L.M.Voll, S.Sonnewald, and U.Sonnewald (2011).
AtHsp70-15-deficient Arabidopsis plants are characterized by reduced growth, a constitutive cytosolic protein response and enhanced resistance to TuMV.
  Plant J, 66, 983-995.  
21278753 T.Böcking, F.Aguet, S.C.Harrison, and T.Kirchhausen (2011).
Single-molecule analysis of a molecular disassemblase reveals the mechanism of Hsc70-driven clathrin uncoating.
  Nat Struct Mol Biol, 18, 295-301.  
20223214 A.Arakawa, N.Handa, N.Ohsawa, M.Shida, T.Kigawa, F.Hayashi, M.Shirouzu, and S.Yokoyama (2010).
The C-terminal BAG domain of BAG5 induces conformational changes of the Hsp70 nucleotide-binding domain for ADP-ATP exchange.
  Structure, 18, 309-319.
PDB codes: 1ugo 1uk5 2d9d 3a8y
20237159 A.K.Mandal, P.A.Gibney, N.B.Nillegoda, M.A.Theodoraki, A.J.Caplan, and K.A.Morano (2010).
Hsp110 chaperones control client fate determination in the hsp70-Hsp90 chaperone system.
  Mol Biol Cell, 21, 1439-1448.  
20679486 B.Eroglu, D.Moskophidis, and N.F.Mivechi (2010).
Loss of Hsp110 leads to age-dependent tau hyperphosphorylation and early accumulation of insoluble amyloid beta.
  Mol Cell Biol, 30, 4626-4643.  
20177057 C.Andréasson, H.Rampelt, J.Fiaux, S.Druffel-Augustin, and B.Bukau (2010).
The endoplasmic reticulum Grp170 acts as a nucleotide exchange factor of Hsp70 via a mechanism similar to that of the cytosolic Hsp110.
  J Biol Chem, 285, 12445-12453.  
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.  
19920147 J.Fiaux, J.Horst, A.Scior, S.Preissler, A.Koplin, B.Bukau, and E.Deuerling (2010).
Structural analysis of the ribosome-associated complex (RAC) reveals an unusual Hsp70/Hsp40 interaction.
  J Biol Chem, 285, 3227-3234.  
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.  
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
20072699 M.Wisniewska, T.Karlberg, L.Lehtiö, I.Johansson, T.Kotenyova, M.Moche, and H.Schüler (2010).
Crystal structures of the ATPase domains of four human Hsp70 isoforms: HSPA1L/Hsp70-hom, HSPA2/Hsp70-2, HSPA6/Hsp70B', and HSPA5/BiP/GRP78.
  PLoS One, 5, e8625.
PDB codes: 3fe1 3gdq 3i33 3iuc 3jxu
20430899 S.J.Hale, S.C.Lovell, Keyzer, and C.J.Stirling (2010).
Interactions between Kar2p and its nucleotide exchange factors Sil1p and Lhs1p are mechanistically distinct.
  J Biol Chem, 285, 21600-21606.  
20953191 S.K.Sharma, P.De los Rios, P.Christen, A.Lustig, and P.Goloubinoff (2010).
The kinetic parameters and energy cost of the Hsp70 chaperone as a polypeptide unfoldase.
  Nat Chem Biol, 6, 914-920.  
20100940 S.Zhang, R.Binari, R.Zhou, and N.Perrimon (2010).
A genomewide RNA interference screen for modifiers of aggregates formation by mutant Huntingtin in Drosophila.
  Genetics, 184, 1165-1179.  
  19908379 Y.Liu, and I.Bahar (2010).
Toward understanding allosteric signaling mechanisms in the ATPase domain of molecular chaperones.
  Pac Symp Biocomput, (), 269-280.  
  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.  
19491934 F.U.Hartl, and M.Hayer-Hartl (2009).
Converging concepts of protein folding in vitro and in vivo.
  Nat Struct Mol Biol, 16, 574-581.  
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.  
19171884 J.Wang, G.W.Farr, C.J.Zeiss, D.J.Rodriguez-Gil, J.H.Wilson, K.Furtak, D.T.Rutkowski, R.J.Kaufman, C.I.Ruse, J.R.Yates, S.Perrin, M.B.Feany, and A.L.Horwich (2009).
Progressive aggregation despite chaperone associations of a mutant SOD1-YFP in transgenic mice that develop ALS.
  Proc Natl Acad Sci U S A, 106, 1392-1397.  
19759005 Keyzer, G.J.Steel, S.J.Hale, D.Humphries, and C.J.Stirling (2009).
Nucleotide binding by Lhs1p is essential for its nucleotide exchange activity and for function in vivo.
  J Biol Chem, 284, 31564-31571.  
19860737 S.Patury, Y.Miyata, and J.E.Gestwicki (2009).
Pharmacological targeting of the Hsp70 chaperone.
  Curr Top Med Chem, 9, 1337-1351.  
18682216 W.A.Hendrickson, and Q.Liu (2008).
Exchange we can believe in.
  Structure, 16, 1153-1155.  
19029896 Z.Xu, R.C.Page, M.M.Gomes, E.Kohli, J.C.Nix, A.B.Herr, C.Patterson, and S.Misra (2008).
Structural basis of nucleotide exchange and client binding by the Hsp70 cochaperone Bag2.
  Nat Struct Mol Biol, 15, 1309-1317.
PDB codes: 3cqx 3d0t
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.