Yusuf Hamied Department of Chemistry

Professor Sophie Jackson

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

The AAA+ protease ClpXP can easily degrade a 3

EM Sivertsson, SE Jackson, LS Itzhaki

– Scientific reports

(2019)

2421

(doi: 10.1038/s41598-018-38173-3)

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 Chem Biol

(2018)

13,

636

(doi: 10.1021/acschembio.7b01039)

Factors affecting the physical stability (aggregation) of peptide therapeutics.

KL Zapadka, FJ Becher, AL Gomes Dos Santos, SE Jackson

– Interface Focus

(2017)

20170030

(doi: 10.1098/rsfs.2017.0030)

Characterization of the Folding of a 5$_{2}$-Knotted Protein Using Engineered Single-Tryptophan Variants

H Zhang, SE Jackson

– Biophysical journal

(2016)

111,

2587

(doi: 10.1016/j.bpj.2016.10.029)

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,

(doi: 10.17863/CAM.7376)

A pH-Induced Switch in Human Glucagon-like Peptide-1 Aggregation Kinetics

KL Zapadka, FJ Becher, S Uddin, PG Varley, S Bishop, AL Gomes Dos Santos, SE Jackson

– J Am Chem Soc

(2016)

138,

16259

(doi: 10.1021/jacs.6b05025)

How to fold intricately: using theory and experiments to unravel the properties of knotted proteins.

SE Jackson, A Suma, C Micheletti

– Curr Opin Struct Biol

(2016)

42,

(doi: 10.1016/j.sbi.2016.10.002)

How to fold intricately: using theory and experiments to unravel the properties of knotted proteins

S Jackson, A Suma, C Micheletti

(2016)

082446

(doi: 10.1101/082446)

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

(2016)

113,

7533

(doi: 10.1073/pnas.1600614113)

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

– J Mol Biol

(2016)

428,

2507

(doi: 10.1016/j.jmb.2016.04.002)