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Department of Chemistry

 
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

Knots in soft condensed matter
I Coluzza, SE Jackson, C Micheletti, MA Miller
– Journal of physics. Condensed matter : an Institute of Physics journal
(2015)
27,
350301
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 ofHelicobacter pylori
L-W Wang, Y-N Liu, P-C Lyu, SE Jackson, S-TD Hsu
– Journal of physics. Condensed matter : an Institute of Physics journal
(2015)
27,
354106
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 reports
(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 NMR assignments of a topologically knotted protein in urea-denatured state
S-JM Hsieh, AL Mallam, SE Jackson, S-TD Hsu
– Biomol NMR Assign
(2014)
8,
439
Erratum to: Backbone 1H, 13C and 15N assignments of YibK and a variant containing a unique cysteine residue at C-terminus in 8 M urea-denatured states
S-JM Hsieh, AL Mallam, SE Jackson, S-TD Hsu
– Biomolecular NMR Assignments
(2014)
8,
443
Backbone NMR assignments of a topologically knotted protein in urea-denatured state.
S-JM Hsieh, AL Mallam, SE Jackson, S-TD Hsu
– Biomolecular NMR Assignments
(2014)
8,
283
Mechanistic insights into the folding of knotted proteins in vitro and in vivo
NCH Lim, SE Jackson
– J Mol Biol
(2015)
427,
248
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Research Group

Research Interest Group

Telephone number

01223 762011
36357 (shared)

Email address

sej13@cam.ac.uk

College

Peterhouse