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Department of Biochemistry

 
Katherine Stott

Organisational and regulatory roles of the disordered proteome.

 

Proteins are often depicted as visually compelling three-dimensional arrangements of alpha helices and beta sheets that recognise their biological partners via structurally complementary surfaces, like a key in a lock. However, a sizeable fraction of proteins are intrinsically disordered, or contain intrinsically-disordered regions, and it is increasingly appreciated that disordered proteins play an essential role in a wide variety of biological processes.

Our research is focused on two areas in which disordered proteins are key players in the organisation and regulation of a molecular assembly: (i) gene expression via chromatin (de)condensation, and (ii) signalling via protein-protein interaction hubs. Our aim in each case is to gain an atomic-level understanding of representative complexes that will inform on the general mechanism, focusing on what is usually the least understood part; the disordered protein. We use a broad methodology, including a range of biophysical methods, solution-state X-ray/neutron scattering and NMR, making extensive use of the Department's in-house biophysics and NMR facilities. Our recent findings include the development of a chromatin model, with which we established the role of 'fuzzy complexes' and liquid-liquid phase separation in the condensation of DNA by linker histone tails, and its regulation by phosphorylation.1

 

Research objectives

  • To establish the drivers of DNA (de)condensation by liquid-liquid phase separation that impact gene expression.

  • To develop a toolkit to describe the structure, molecular recognition processes, dynamics and functional impact of 'fuzzy complexes'.

  • To understand how disordered scaffold proteins assemble and regulate signalling complexes, and to develop molecular tools to disrupt them (in collaboration with the McNaughton Group at King's College London).

 

Key publications

Watson M, Stott K (2019). Disordered domains in chromatin-binding proteins. Essays Biochem., 63(1):147-156. doi: 10.1042/EBC20180068

1 Turner AL, Watson M, Wilkins OG, Cato L, Travers A, Thomas JO, Stott K (2018). Highly disordered histone H1-DNA model complexes and their condensates. Proc. Natl. Acad. Sci. U.S.A., 115(47):11964-11969. doi: 10.1073/pnas.1805943115

Stott K, Watson M, Bostock MJ, Mortensen SA, Travers A, Grasser KD, Thomas JO (2014). Structural insights into the mechanism of negative regulation of single-box high mobility group proteins by the acidic tail domain. J. Biol. Chem., 289(43):29817-29826. doi: 10.1074/jbc.M114.591115

Btesh J, Fischer MJM, Stott K, McNaughton PA (2013). Mapping the binding site of TRPV1 on AKAP79: implications for inflammatory hyperalgesia. J. Neurosci., 33(21):9184-9193. doi: 10.1523/JNEUROSCI.4991-12.2013

Thomas JO, Stott K (2012). H1 and HMGB1: modulators of chromatin structure. Biochem. Soc. Trans., 40(2):341-346. doi: 10.1042/BST20120014

Contact details

Research Group Leader  Katherine Stott

Facility Website  Biophysics Facility Manager

Email  ks123@cam.ac.uk

Location  Sanger Building

Opportunities

The Stott Group is accepting enquiries from prospective interns, undergraduate students and postgraduate students.