skip to content

Yusuf Hamied Department of Chemistry

 
Portrait of sej13

Professor of Chemical and Molecular Biology

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

Watch Professor Jackson discuss her research

Take a tour of the Jackson Lab

Publications

Toward Rapid Aspartic Acid Isomer Localization in Therapeutic Peptides Using Cyclic Ion Mobility Mass Spectrometry
K Gibson, DA Cooper-Shepherd, E Pallister, SE Inman, SE Jackson, V Lindo
– Journal of the American Society for Mass Spectrometry
(2022)
The Amyloid Fibril-Forming β-Sheet Regions of Amyloid β and α-Synuclein Preferentially Interact with the Molecular Chaperone 14-3-3ζ.
DM Williams, DC Thorn, CM Dobson, S Meehan, SE Jackson, JM Woodcock, JA Carver
– Molecules (Basel, Switzerland)
(2021)
26,
6120
Interconversion of Unexpected Thiol States Affects the Stability, Structure, and Dynamics of Antibody Engineered for Site-Specific Conjugation
CT Orozco, MJ Edgeworth, PWA Devine, AR Hines, O Cornwell, C Thompson, X Wang, JJ Phillips, P Ravn, SE Jackson, NJ Bond
– Bioconjugate Chemistry
(2021)
32,
1834
Interconversion of unexpected thiol states affects stability, structure and dynamics in engineered antibody for site-specific conjugation
CT Orozco, MJ Edgeworth, PWA Devine, AR Hines, O Cornwell, X Wang, JJ Phillips, P Ravn, SE Jackson, NJ Bond
(2020)
Why are there knots in proteins?
SE Jackson
– Contemporary Mathematics
(2020)
746,
129
The AAA+ protease ClpXP can easily degrade a 31 and a 52-knotted protein.
EM Sivertsson, SE Jackson, LS Itzhaki
– Scientific reports
(2019)
9,
2421
Hsp70 Inhibits the Nucleation and Elongation of Tau and Sequesters Tau Aggregates with High Affinity.
F Kundel, S De, P Flagmeier, MH Horrocks, M Kjaergaard, SL Shammas, SE Jackson, CM Dobson, D Klenerman
– ACS Chemical Biology
(2018)
13,
636
Factors affecting the physical stability (aggregation) of peptide therapeutics
KL Zapadka, FJ Becher, AL Gomes Dos Santos, SE Jackson
– Interface focus
(2017)
7,
20170030
Characterization of the Folding of a 5$_{2}$-Knotted Protein Using Engineered Single-Tryptophan Variants
H Zhang, SE Jackson
– Biophys J
(2016)
111,
2587
pyFRET: A Python Library for Single Molecule Fluorescence Data Analysis
RR Murphy, SE Jackson, D Klenerman
– Proceedings of the 7th European Conference on Python in Science (EuroSciPy 2014)
(2016)
1412,
59
  • 1 of 12
  • >

Research Group

Research Interest Group

Telephone number

01223 762011
36357 (shared)

Email address

sej13@cam.ac.uk

College

Peterhouse