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PMID: 18660820 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The structure of CCT-Hsc70 NBD suggests a mechanism for Hsp70 delivery of substrates to the chaperonin.

Nature structural & molecular biology ·Vol. 15 ·No. 8 ·2008-08-00 ·Pages 858-64

Cuéllar J, Martín-Benito J, Scheres SH, Sousa R, Moro F, López-Viñas E, Gómez-Puertas P, Muga A, Carrascosa JL, Valpuesta JM

Abstract

Chaperones, a group of proteins that assist the folding of other proteins, seem to work in a coordinated manner. Two major chaperone families are heat-shock protein families Hsp60 and Hsp70. Here we show for the first time the formation of a stable complex between chaperonin-containing TCP-1 (CCT) and Hsc70, two eukaryotic representatives of these chaperone families. This interaction takes place between the apical domain of the CCT beta subunit and the nucleotide binding domain of Hsc70, and may serve to deliver the unfolded substrate from Hsc70 to the substrate binding region of CCT. We also show that a similar interaction does not occur between their prokaryotic counterparts GroEL and DnaK, suggesting that in eukarya the two types of chaperones have evolved to a concerted action that makes the folding task more efficient.

MeSH Terms
Amino Acid Sequence Animals Cattle Chaperonin Containing TCP-1 Chaperonins/chemistry Escherichia coli Proteins/chemistry HSC70 Heat-Shock Proteins/metabolism HSP70 Heat-Shock Proteins/chemistry Molecular Chaperones/chemistry Molecular Sequence Data Protein Binding Protein Conformation Protein Isoforms Protein Structure, Tertiary Sequence Homology, Amino Acid
Chemicals
Escherichia coli Proteins HSC70 Heat-Shock Proteins HSP70 Heat-Shock Proteins Molecular Chaperones Protein Isoforms Chaperonin Containing TCP-1 Chaperonins dnaK protein, E coli
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Cuéllar Jorge
Centro Nacional de Biotecnología, CSIC, Campus de la Universidad Autónoma de Madrid, Darwin, 3, 28049 Madrid, Spain.
Martín-Benito Jaime
Scheres Sjors H W
Sousa Rui
Moro Fernando
López-Viñas Eduardo
Gómez-Puertas Paulino
Muga Arturo
Carrascosa José L
Valpuesta José M
References (44)
44 references, click to expand
  1. Sequential ATP-induced allosteric transitions of the cytoplasmic chaperonin containing TCP-1 revealed by EM analysis.
    Nat Struct Mol Biol. 2005 Mar;12(3):233-7 PMID: 15696173
  2. Divergent substrate-binding mechanisms reveal an evolutionary specialization of eukaryotic prefoldin compared to its archaeal counterpart.
    Structure. 2007 Jan;15(1):101-10 PMID: 17223536
  3. T-Coffee: A novel method for fast and accurate multiple sequence alignment.
    J Mol Biol. 2000 Sep 8;302(1):205-17 PMID: 10964570
  4. Review: postchaperonin tubulin folding cofactors and their role in microtubule dynamics.
    J Struct Biol. 2001 Aug;135(2):219-29 PMID: 11580271
  5. Thermodynamic and structural analysis of the folding/unfolding transitions of the Escherichia coli molecular chaperone DnaK.
    J Mol Biol. 1993 Jul 20;232(2):680-92 PMID: 8102181
  6. ProtTest: selection of best-fit models of protein evolution.
    Bioinformatics. 2005 May 1;21(9):2104-5 PMID: 15647292
  7. A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood.
    Syst Biol. 2003 Oct;52(5):696-704 PMID: 14530136
  8. Prefoldin, a chaperone that delivers unfolded proteins to cytosolic chaperonin.
    Cell. 1998 May 29;93(5):863-73 PMID: 9630229
  9. Chaperone network in the yeast cytosol: Hsp110 is revealed as an Hsp70 nucleotide exchange factor.
    EMBO J. 2006 Jun 7;25(11):2510-8 PMID: 16688211
  10. T-complex polypeptide-1 is a subunit of a heteromeric particle in the eukaryotic cytosol.
    Nature. 1992 Jul 16;358(6383):249-52 PMID: 1630492
  11. PhLP3 modulates CCT-mediated actin and tubulin folding via ternary complexes with substrates.
    J Biol Chem. 2006 Mar 17;281(11):7012-21 PMID: 16415341
  12. Interdomain interaction through helices A and B of DnaK peptide binding domain.
    FEBS Lett. 2003 Jan 2;533(1-3):119-23 PMID: 12505170
  13. The Hsp70 and Hsp60 chaperone machines.
    Cell. 1998 Feb 6;92(3):351-66 PMID: 9476895
  14. A novel protein complex promoting formation of functional alpha- and gamma-tubulin.
    EMBO J. 1998 Feb 16;17(4):952-66 PMID: 9463374
  15. The Hsp70 and TRiC/CCT chaperone systems cooperate in vivo to assemble the von Hippel-Lindau tumor suppressor complex.
    Mol Cell Biol. 2003 May;23(9):3141-51 PMID: 12697815
  16. Eukaryotic chaperonin CCT stabilizes actin and tubulin folding intermediates in open quasi-native conformations.
    EMBO J. 2000 Nov 15;19(22):5971-9 PMID: 11080144
  17. Structural basis of interdomain communication in the Hsc70 chaperone.
    Mol Cell. 2005 Nov 23;20(4):513-24 PMID: 16307916
  18. Structure of eukaryotic prefoldin and of its complexes with unfolded actin and the cytosolic chaperonin CCT.
    EMBO J. 2002 Dec 2;21(23):6377-86 PMID: 12456645
  19. Characterization of Hsp70 binding and nucleotide exchange by the yeast Hsp110 chaperone Sse1.
    Biochemistry. 2006 Dec 19;45(50):15075-84 PMID: 17154545
  20. Disentangling conformational states of macromolecules in 3D-EM through likelihood optimization.
    Nat Methods. 2007 Jan;4(1):27-9 PMID: 17179934
  21. XMIPP: a new generation of an open-source image processing package for electron microscopy.
    J Struct Biol. 2004 Nov;148(2):194-204 PMID: 15477099
  22. Molecular chaperones of the Hsp110 family act as nucleotide exchange factors of Hsp70s.
    EMBO J. 2006 Jun 7;25(11):2519-28 PMID: 16688212
  23. Chaperonin TRiC promotes the assembly of polyQ expansion proteins into nontoxic oligomers.
    Mol Cell. 2006 Sep 15;23(6):887-97 PMID: 16973440
  24. Maximum-likelihood multi-reference refinement for electron microscopy images.
    J Mol Biol. 2005 Apr 22;348(1):139-49 PMID: 15808859
  25. EMAN: semiautomated software for high-resolution single-particle reconstructions.
    J Struct Biol. 1999 Dec 1;128(1):82-97 PMID: 10600563
  26. The crystal structure of the bacterial chaperonin GroEL at 2.8 A.
    Nature. 1994 Oct 13;371(6498):578-86 PMID: 7935790
  27. The chaperonin TRiC controls polyglutamine aggregation and toxicity through subunit-specific interactions.
    Nat Cell Biol. 2006 Oct;8(10):1155-62 PMID: 16980959
  28. Successive action of DnaK, DnaJ and GroEL along the pathway of chaperone-mediated protein folding.
    Nature. 1992 Apr 23;356(6371):683-9 PMID: 1349157
  29. Insights into Hsp70 chaperone activity from a crystal structure of the yeast Hsp110 Sse1.
    Cell. 2007 Oct 5;131(1):106-20 PMID: 17923091
  30. Peptide mass fingerprinting of chaperonin-containing TCP-1 (CCT) and copurifying proteins.
    FASEB J. 1996 Jan;10(1):137-47 PMID: 8566534
  31. Folding of nascent polypeptide chains in a high molecular mass assembly with molecular chaperones.
    Nature. 1994 Jul 14;370(6485):111-7 PMID: 8022479
  32. The chaperone cofactor Hop/p60 interacts with the cytosolic chaperonin-containing TCP-1 and affects its nucleotide exchange and protein folding activities.
    J Biol Chem. 1998 Nov 6;273(45):29475-80 PMID: 9792653
  33. Multi-resolution contour-based fitting of macromolecular structures.
    J Mol Biol. 2002 Mar 29;317(3):375-84 PMID: 11922671
  34. Eukaryotic type II chaperonin CCT interacts with actin through specific subunits.
    Nature. 1999 Dec 9;402(6762):693-6 PMID: 10604479
  35. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
    Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 PMID: 9254694
  36. Phosducin-like protein acts as a molecular chaperone for G protein betagamma dimer assembly.
    EMBO J. 2005 Jun 1;24(11):1965-75 PMID: 15889144
  37. Elucidation of the subunit orientation in CCT (chaperonin containing TCP1) from the subunit composition of CCT micro-complexes.
    EMBO J. 1997 Jul 16;16(14):4311-6 PMID: 9250675
  38. The crystal structure of the asymmetric GroEL-GroES-(ADP)7 chaperonin complex.
    Nature. 1997 Aug 21;388(6644):741-50 PMID: 9285585
  39. Cytosolic chaperonin prevents polyglutamine toxicity with altering the aggregation state.
    Nat Cell Biol. 2006 Oct;8(10):1163-70 PMID: 16980958
  40. Structure of the complex between the cytosolic chaperonin CCT and phosducin-like protein.
    Proc Natl Acad Sci U S A. 2004 Dec 14;101(50):17410-5 PMID: 15583139
  41. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice.
    Nucleic Acids Res. 1994 Nov 11;22(22):4673-80 PMID: 7984417
  42. Folding of the glucocorticoid receptor by the reconstituted Hsp90-based chaperone machinery. The initial hsp90.p60.hsp70-dependent step is sufficient for creating the steroid binding conformation.
    J Biol Chem. 1997 May 16;272(20):13047-54 PMID: 9148915
  43. In vivo newly translated polypeptides are sequestered in a protected folding environment.
    EMBO J. 1999 Jan 4;18(1):85-95 PMID: 9878053
  44. Crystal structure of the C-terminal 10-kDa subdomain of Hsc70.
    J Biol Chem. 2003 Aug 8;278(32):30311-6 PMID: 12773536
Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.1464
Published
2008-08-00
Epub
2008-00-27
Pages
858-64
Language
English
Region
United States
NLM ID
101186374
PMCID
PMC4449276
Subset
IM
Grants
NIGMS NIH HHS · R01 GM052522 · United States
External Links
PubMed source DOI: 10.1038/nsmb.1464 PMC Full Text View journal details
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