Chaperones and protein disaggregation

Saibil group, ISMB
Birkbeck College London

A liquid to solid phase transition underlying pathological huntingtin exon1 aggregation. Peskett, TR, Rau, F, O’Driscoll, J, Patani, R, Saibil, HR (2018) Molec. Cell,
Structural pathway of regulated substrate transfer and threading through an Hsp100 disaggregase. Deville, C, Carroni, M, Franke, KB, Topf, M, Bukau, B, Mogk, A, & Saibil, HR (2017) Science Advances 3:e1701726.
amyloid fibril +
Human Hsp70 disaggregase reverses Parkinson's-linked alpha-synuclein amyloid fibrils. Gao, X, Carroni, M, Nussbaum-Krammer, C, Mogk, A Nillegoda, NB, Szlachcic, A, Guilbride, DL, Saibil, HR, Mayer MP & Bukau, B (2015) Mol. Cell 59, 781-793.
Head-to-tail interactions of the coiled-coil domains regulate ClpB activity and cooperation with Hsp70 in protein disaggregation. Carroni, M, Kummer, E, Oguchi, Y, Wendler, P, Clare, DK, Sinning, I, Kopp, J, Mogk, A, Bukau, B & Saibil, HR (2014) eLife 3:e02481
ClpB-Hsp70 model
Chaperone machines for protein folding, unfolding and disaggregation. Saibil, HR (2013) Nature Rev. Mol. Cell. Biol. 14, 630-642.
Cell 2012
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.
Newly folded substrates inside the molecular cage of the HtrA chaperone DegQ. Malet, H, Canellas, F, Sawa, J, Yan, J, Thalassinos, K, Ehrmann, M, Clausen, T & Saibil, HR (2012) Nature Struct. Mol. Biol. 19, 152-157.
GroEL-gp31-gp23 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.
Group 2
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,
Topologies of a substrate protein bound to the chaperonin GroEL. Elad, N, Farr, GW, Clare, DK, Orlova, EV, Horwich, AL & Saibil, HR (2007) Mol. Cell 26, 415-426.
Multiple distinct assemblies reveal conformational flexibility in the small heat shock protein Hsp26. White, HE, Orlova, EV, Chen, S, Wang, L, Ignatiou, A, Gowen, B, Stromer, T, Franzmann, TM, Haslbeck, M, Buchner, J & Saibil, HR (2006) Structure14, 1197-1204.
GroE allostery 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.
GroEL E461K
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.
ATP-bound states of GroEL captured by cryo-electron microscopy, Ranson et al. (2001) Cell 107, 869-879.
Cell 1996
The chaperonin ATPase cycle: mechanism of allosteric switching and movements of substrate-binding domains in GroEL, Roseman et al. (1996) Cell 87, 241-251.
GroE movieMovie of ATPase cycle
GroE 1994
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.

Birkbeck EM group
Helen Saibil