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Dr Sophie Jackson

Portrait of sej13

Protein Folding and Assembly

Our research focuses on different aspects of how proteins fold and how large protein complexes assemble. Projects cover diverse areas including biophysics, molecular biology (including protein engineering) and chemical biology. Current projects include:

How does a knotted protein fold?

Recently, a remarkable new class of proteins have been discovered which have deep topological knots formed by the polypeptide backbone. These structures represent a new challenge for the protein folding community - not only has the protein to fold but in doing so it must also knot. We are studying the folding pathways of several knotted proteins, including YibK shown on the right, using a combination of experimental and computational techniques.

How do molecular chaperones work to assembly large molecular complexes?

Heat shock protein 90 (Hsp90) is a highly abundant and important protein in our cells which is the target of a new class of anti-tumour agents. It plays a key role in the assembly of a number of cellular complexes which are critical in cellular signal transduction pathways. We are combining a large number of biophysical techniques to understand the mode of action of Hsp90.

Single molecule studies on the folding of a large β-barrel protein.

The green fluorescent protein (GFP) first isolated from jellyfish is a protein with unique spectroscopic properties. A cyclisation and oxidation of the polypeptide backbone results in the formation of a chromophore which is highly fluorescent. In collaboration with the Klenerman group are using these special features of GFP to study the folding of this protein at a single molecule level.

Selected Publications

  • Mallam, A.L., Rogers, J.M. and Jackson, S.E. (2010) Proc. Natl. Acad. Sci. 107, 8189-8194. Experimental detection of knotted conformations in denatured proteins
  • Hsu, D., Blaser, G., Behrens, C., Cabrita, LD., Dobson, C.M. and Jackson, S.E. (2010) J. Biol. Chem. 285, 4859-4869. Folding Study of Venus Reveals a Strong Ion Dependence of its Yellow Fluorescence under Mildly Acidic Conditions
  • Onuoha, S.C., Coulstock, E.C., Grossmann, J.G. and Jackson, S.E. (2008) J. Mol. Biol. 379, 732-744. Structural studies on the co-chaperone Hop and its complexes with Hsp90
  • Mallam, A.L., Onuoha, S.C., Grossmann, J.G. and Jackson, S.E. (2008) Molecular Cell 30, 642-648. Knotted fusion proteins reveal unexpected possibilities in protein folding
  • Orte, A., Craggs, T.D., White, S. Jackson, S.E. and Klenerman, D. (2008) J. Am.Chem.Soc. 130, 7898-7907. Evidence of an intermediate and parallel pathways in protein unfolding using single-molecule fluorescence

Publications

Knotting and unknotting of a protein in single molecule experiments.
F Ziegler, NCH Lim, SS Mandal, B Pelz, W-P Ng, M Schlierf, SE Jackson, M Rief
– Proceedings of the National Academy of Sciences of the United States of America
(2016)
113,
7533
The Knotted Protein UCH-L1 Exhibits Partially Unfolded Forms under Native Conditions that Share Common Structural Features with Its Kinetic Folding Intermediates.
S-C Lou, S Wetzel, H Zhang, EW Crone, Y-T Lee, SE Jackson, S-TD Hsu
– Journal of molecular biology
(2016)
428,
2507
Chaperome screening leads to identification of Grp94/Gp96 and FKBP4/52 as modulators of the α-synuclein-elicited immune response.
A Labrador-Garrido, M Cejudo-Guillén, S Daturpalli, MM Leal, R Klippstein, EJ De Genst, J Villadiego, JJ Toledo-Aral, CM Dobson, SE Jackson, D Pozo, C Roodveldt
– The FASEB Journal
(2016)
30,
564
Molecular knots in biology and chemistry
NCH Lim, SE Jackson
– Journal of Physics: Condensed Matter
(2015)
27,
354101
Comparative analysis of the folding dynamics and kinetics of an engineered knotted protein and its variants derived from HP0242 of Helicobacter pylori.
L-W Wang, Y-N Liu, P-C Lyu, SE Jackson, S-TD Hsu
– Journal of Physics: Condensed Matter
(2015)
27,
354106
Knots in soft condensed matter.
I Coluzza, SE Jackson, C Micheletti, MA Miller
– Journal of Physics: Condensed Matter
(2015)
27,
350301
Folding of nascent chains of knotted proteins
SE Jackson, NC Lim, AL Mallam, DS Hsu, LS Itzhaki, E Siverstsson
– EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2015)
44,
S203
Hsp70 forms antiparallel dimers stabilized by post-translational modifications to position clients for transfer to Hsp90.
N Morgner, C Schmidt, V Beilsten-Edmands, I-O Ebong, NA Patel, EM Clerico, E Kirschke, S Daturpalli, SE Jackson, D Agard, CV Robinson
– Cell Rep
(2015)
11,
759
Hsp70 Forms Antiparallel Dimers Stabilized by Post-translational Modifications to Position Clients for Transfer to Hsp90
N Morgner, C Schmidt, V Beilsten-Edmands, IO Ebong, NA Patel, EM Clerico, E Kirschke, S Daturpalli, SE Jackson, D Agard, CV Robinson
– Cell Reports
(2015)
11,
759
Backbone 1H, 13C and 15N assignments of YibK and avariant containing a unique cysteine residue at C-terminus in 8 M urea-denatured states [corrected].
S-JM Hsieh, AL Mallam, SE Jackson, S-TD Hsu
– Biomolecular NMR Assignments
(2014)
8,
439
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Research Group

Research Interest Group

Telephone number

01223 336357 (shared)
01223 762011

Email address

sej13@cam.ac.uk

College

Peterhouse