Molecular basis of neurotransmission – cryo-EM structural and functional investigation of the human serotonin receptor in a lipid environment

Paula Booth (primary)
Chemistry
King's College London
Claudine Bisson (secondary)
ISMB, Birkbeck College London & Centre for Ultrastructural Imaging, King’s College London
Birkbeck College London & King's College London

Abstract

Serotonin is a vital component of the human nervous system with the neurotransmitter playing a variety of roles in physiology including sensory perception, mood, cognition and memory. Perturbation of the serotonergic system is implicated in anxiety disorders and serotonin transporters are notable drug targets for antidepressants and antipsychotics. This project aims to increase molecular-level understanding of these neurotransmitter transporters through structure and function study. Cryo-electron microscopy, cryo-EM, will be undertaken on the human serotonin transporter in lipid nanodiscs following direct extraction from the membrane using a novel polymer, DIBMA, method.


References

1. M. V. Dilworth, H. E. Findlay and P. J. Booth, Biochim Biophys Acta Biomembr, 2021, 1863, 183602.
2. E. Reading, Z. Hall, C. Martens, T. Haghighi, H. Findlay, Z. Ahdash, A. Politis and P. J. Booth, Angew Chem Int Ed Engl, 2017, 56, 15654-15657.
3. J. A. Coleman, E. M. Green and E. Gouaux, Nature, 2016, 532, 334-339.
4. S. Rawson, C. Bisson, D. L. Hurdiss, A. Fazal, M. J. McPhillie, S. E. Sedelnikova, P. J. Baker, D. W. Rice and S. P. Muench, Proc Natl Acad Sci U S A, 2018, 115, 1795-1800.
5. G. A. Pellowe, H. E. Findlay, K. Lee, T. M. Gemeinhardt, L. R. Blackholly, E. Reading and P. J. Booth, Biochemistry, 2020, 59, 2764-2775.


BBSRC Area
Molecules, cells and industrial biotechnology
Area of Biology
Chemical BiologyStructural Biology
Techniques & Approaches
BiochemistryBiophysicsChemistryImage ProcessingMolecular Biology