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Understanding how intrinsic disorder drives the formation of fuzzy protein complexes and tunes protein function


Project Description

Intrinsically disordered protein regions lack stable structure and instead move stochastically through an ensemble of conformations. Where it was once thought that absence of structure meant absence of function, it is now known that intrinsic disorder playa a critical role in cellular signalling systems. This project uses the co-receptor system for the plant hormone auxin as a model
to understand how ordered regulation of protein function can arise from structural disorder.

Auxin is probably the most interesting molecule in biology. Via the formation of the TIR1-auxin-Aux/IAA co-receptor complex, auxin regulates virtually every aspect of plant development. Our recent work has shown that half of the Aux/IAA protein component, including the motif that interacts with the Fbox protein TIR1, is intrinsically disordered. This disorder is retained during the interaction and so the co-receptor complex is known as a ‘fuzzy complex’. We have also shown that the conformational ambiguity of the Aux/IAA is central to this process of complex formation. This project would allow you to build of these exciting discoveries and join a rapidly developing field, using techniques including nuclear magnetic resonance (NMR) and Cryo-electron microscopy (Cryo-EM) to address an intellectually intriguing and economically important question in structural and plant biology.

Funding Notes

White Rose BBSRC DTP in Mechanistic Biology
4 year fully-funded programme of integrated research and skills training, starting Oct 2020:
• Research Council Stipend
• UK/EU Tuition Fees
• Conference and research funding

Requirements:
At least a 2:1 honours degree or equivalent. We welcome students with backgrounds in biological, chemical or physical sciences, or mathematical backgrounds with an interest in biological questions.

EU candidates require 3 years of UK residency to receive full studentship

The DTP will appoint a number of candidates via a competitive process.

View Website

Prospective candidates are encouraged to contact Stefan Kepinski () to discuss the project.

References

Ramans Harborough, S, Kalverda, A.P., Thompson, G.S., Kieffer, M., Kubes, M., Quareshy, M., Prusinska, J., Hayashi, K., Napier, R.M., Manfield, I.M., Kepinski, S. (2019) A fuzzy encounter complex precedes formation of the fully-engaged TIR1-Aux/IAA auxin co-receptor system. bioRxiv doi: https://doi.org/10.1101/781922

Wieteska, L., Shahidi, S., Zhuravleva A. (2017) Allosteric fine-tuning of the conformational equilibrium poises the chaperone BiP for post-translational regulation. eLife;6:e29430.

Hesketh, E.L, Saunders, K., Fisher, C., Potze, J., Stanley, J., Lomonossoff, G.P. & Ranson, N.A. (2018). The 3.3 Å structure of a plant geminivirus using cryo-EM. Nature Communications, 9, 2369. DOI:10.1038/s41467-018-04793-6

Wang, R., Zhang, Y., Kieffer, M., Yu, H., Kepinski, S., and Estelle, M. (2016) HSP90 regulates temperature-dependent seedling growth by stabilizing the auxin receptor F-box protein TIR1. Nature Communications 7:10269. doi: 10.1038/ncomms10269.

How good is research at University of Leeds in Biological Sciences?

FTE Category A staff submitted: 60.90

Research output data provided by the Research Excellence Framework (REF)

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