Molecular Chaperone Group 

School of Crystallography
Birkbeck College London

GroEL   Other chaperones   Links

Helen Saibil
Dan Clare, Marta Carroni, Jonathan O'Driscoll

Former group members
Shaoxia Chen (MRC-LMB, Cambridge), Alan Roseman (University of Manchester), Guy Schoehn (EMBL Grenoble), Corinne Smith (University of Warwick), Neil Ranson (Leeds University), David Wright (NIMR), Nadav Elad (Weizmann Institute), Petra Wendler (Gene Center, LMU, Munich), R Natesh (Indian Institute of Science, Thiruvananthapuram), Helene Malet (EMBL Grenoble)

GroE chaperonins

Our early work on cryo-EM of chaperonins was a collaboration with Tony Clarke, Steve Burston and Neil Ranson (University of Bristol) and was published in Location of a folding protein and shape changes in GroEL-GroES complexes imaged by cryo-electron microscopy, Chen et al. (1994) Nature 371, 261-264.
Subsequent work in collaboration with Art Horwich, Wayne Fenton and their colleagues at Yale launched a more complete structural characterisation of the chaperonin-nucleotide cycle and was published as The chaperonin ATPase cycle: mechanism of allosteric switching and movements of substrate-binding domains in GroEL, Roseman et al. (1996) Cell 87, 241-251.

GroEL-nucleotide structures at 30 Å resolution
GroEL-GroES-nucleotide structures at 30 Å resolution
Atomic structure of GroEL inter-ring contacts: charge pairs (blue/red), the alpha-helix (green) connecting the front contact to the ATP binding site and the bound ATP (lilac), fitted into GroEL-ADP and ATP structures from cryo EM (white wire mesh surfaces).
Movies of the GroEL ATPase cycle
Images © Cell Press 1996

Our cryo-EM study on the R197A mutant of GroEL in collaboration with Amnon Horovitz and colleagues at the Weizmann Institute described the structure of different allosteric states at low resolution and was published in Structural basis of allosteric changes in the GroEL mutant Arg197-Ala. White et al. (1997) Nature Struct. Biol. 4, 690-694.

A further analysis of the effects of nucleotide binding in the GroEL-GroES system is described in GroEL-GroES cycling: ATP and nonnative polypeptide direct alternation of folding-active rings. Rye et al. (1999) Cell 97, 325-338.

Article on Cell website
Movies and additional methods on Cell website

Images © Cell Press 1999
Low resolution (~30 Å) structures of GroEL heptamers expressed as a single polypeptide chain have been described in Multivalent binding of non-native substrate proteins by the chaperonin GroEL, Farr et al. (2000) Cell 100, 561-573.
Article on Cell website.
Images © Cell Press 2000
Further work focussed on higher resolution structures of the GroEL-ATP complex, with a study on the wild type protein published in The ATP-bound State of the E. Coli Chaperonin GroEL Studied by Cryo-Electron Microscopy, Roseman et al. (2001) J. Struct. Biol. 135, 115-125.
Article on Journal of Structural Biology website.
Images © Academic Press 2001

Subsequently, higher resolution structures of unliganded GroEL, GroEL-ATP (using the D398A mutant of GroEL) and GroES-ADP-GroEL-ATP complex have been determined: ATP-bound states of GroEL captured by cryo-electron microscopy, Ranson et al. (2001) Cell 107, 869-879.
Summary Full Text PDF Supplementary Material
EM structures of unliganded GroEL and GroEL(D398A)-ATP
EM structure of GroES-ADP7-GroEL-ATP7

Images © Cell Press 2001

Allostery and protein substrate conformational change during GroEL/GroES-mediated protein folding. Saibil HR, Horwich AL, & Fenton WA (2002) Adv Protein Chem. 59, 45-72.

Folding with and without encapsulation by cis- and trans-only GroEL-GroES complexes. Farr GW, Fenton WA, Chaudhuri TK, Clare DK, Saibil HR, Horwich AL (2003) EMBO J. 22, 3220-3230.

The chaperonin folding machine. Saibil, HR & Ranson, NA (2002) Trends in Biochem. Sci. 27, 627-632. A mutant chaperonin with rearranged inter-ring electrostatic contacts and temperature-sensitive dissociation. Sewell, BT, Best, RB, Chen, S, Roseman, AM, Farr, GW, Horwich, AL & Saibil, HR (2004) Nature Struct. Mol. Biol. 11, 1128-1133.

Allosteric signalling of ATP hydrolysis in GroEL-GroES complexes. Ranson, NA, Clare, DK, Farr, GW, Houldershaw, D, Horwich AL & Saibil, HR (2006) Nature Struct. Mol. Biol. 13, 147-152.
An expanded protein folding cage in the GroEL-gp31 complex. Clare, D, Bakkes, PJ, van Heerikhuizen, H, Saskia M van der Vies, S, Saibil, HR (2006) J Mol Biol 358, 905-911.
Toplogies of a substrate protein bound to the chaperonin GroEL. Elad, N, Farr, GW, Clare, D, Orlova, EV, Horwich, AL & Saibil, HR (2007) Mol. Cell 26, 415-426. Chaperonin complex with a newly folded substrate protein encapsulated in the folding chamber. Clare, DK, Bakkes, P, van Heerikhuizen, H, van der Vies, SM & Saibil, HR (2009) Nature 457, 107-111.
ATP-triggered conformational changes delineate substrate-binding and -folding mechanics of the GroEL chaperonin. Clare, DK, Vasishtan, D, Stagg, S, Quispe, J, Farr, GW, Topf, M, Horwich, AL & Saibil, HR (2012) Cell 149, 113-123.

Other Chaperones and quality control

A small heat shock protein stably binds heat-denatured model substrates and can maintain a substrate in folding competent state. Lee, GJ, Roseman, AM, Saibil, HR & Vierling, E (1997) EMBO J. 16, 659-671.
Article on EMBO Journal website.

For a review of the GroE chaperonins see Chaperonins, Ranson, NA, White, HE & Saibil, HR (1998) Biochem J. 333, 233-242.
Article on Biochem. J. website.
Images © Portland Press 1998.

Hsp26: a temperature-regulated chaperone. Haslbeck, M, Walke, S, Stromer, T, Ehrnsperger, M, White, HE, Chen, S, Saibil, HR & Buchner, J (1999) EMBO J. 18, 6744-6751.
Article on EMBO Journal website.

© EMBO 1999

Molecular chaperones: containers and surfaces for folding, stabilising or unfolding proteins. Saibil, HR (2000) Current Opinion in Struct. Biol. 10, 251-258.

Three conformations of an archaeal chaperonin, TF55 from Sulfolobus shibatae. Schoehn G, Quaite-Randall E, Jimenez JL, Joachimiak A, Saibil HR (2000) J Mol. Biol. 296, 813-819.
Article on Journal of Molecular Biology website.
© Academic Press 2001

Domain rotations between open, closed and bullet-shaped forms of the thermosome, an archaeal chaperonin . Schoehn G., Hayes M., Cliff M., Clarke A.R. & Saibil H.R. (2000) J. Mol. Biol. 301, 323-332.
Article on Journal of Molecular Biology website

A domain in the N-terminal part of Hsp26 is essential for chaperone function and oligomerization. Haslbeck, M, Ignatiou, A, Saibil, HR, Helmich, S, Frenzl, E, Stromer, T & Buchner, J (2004) J. Mol. Biol. 343, 445-455.

Dodecameric structure of the small heat shock protein ACR1 from Mycobacterium tuberculosis. Kennaway CK, Benesch JL, Gohlke U, Wang L, Robinson CV, Orlova EV, Saibil HR, Keep NH (2005) J Biol Chem. 280, 33419-33425.
Article on JBC website.

Multiple distinct assemblies reveal conformational flexibility in the small heat shock protein Hsp26. Helen E. White, Elena V. Orlova, Shaoxia Chen, Luchun Wang, Athanasios Ignatiou, Brent Gowen, Thusnelda Stromer, Titus M. Franzmann, Martin Haslbeck, Johannes Buchner, Helen R. Saibil (2006) Structure 14, 1197-1204.

Chaperone machines in action. Saibil, HR (2008) Curr. Opin. Struct. Biol. 18, 35-42.

Structural basis for the regulated protease and chaperone function of DegP. Krojer, T, Sawa, J, Schafer, E, Saibil, HR, Ehrmann, M & Clausen, T (2008) Nature 453, 885-890.

Multiple states of a nucleotide-bound group 2 chaperonin. Clare, DK, Stagg, S, Quispe, J, Farr, GW, Horwich, AL & Saibil, HR (2008) Structure 16, 528-534. Atypical AAA+ subunit packing creates an expanded cavity for disaggregation by the protein-remodeling factor Hsp104. Wendler, P, Shorter, J, Plisson, C, Cashikar, AG, Lindquist, S, Saibil, HR (2007) Cell 31, 1366-1377.
Motor mechanism for protein threading through Hsp104. Wendler, P, Shorter, J, Snead, D, Plisson, C, Clare, DK, Lindquist, S, Saibil, HR (2009) Mol. Cell 34, 81-92.
Malet H, Topf M, Clare DK, Ebert J, Bonneau F, Basquin J, Drazkowska K, Tomecki R, Dziembowski A, Conti E, Saibil HR, Lorentzen E. (2010) RNA channelling by the eukaryotic exosome. EMBO Rep. 11, 936-942. Malet, H, Canellas, F, Sawa, J, Yan, J, Thalassinos, K, Ehrmann, M, Clausen, T & Saibil, HR (2012) Newly folded substrates inside the molecular cage of the HtrA chaperone DegQ, Nature Struct. Mol. Biol. 19, 152-157.


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