Sarah Lummis

Characterisation of Cys-loop receptors.

The Cys-loop or pentameric ligand-gated ion channel (pLGIC) family of neurotransmitter-gated channels provide rapid signal transmission at neuronal synapses. Dysfunctional Cys-loop receptors are responsible for a range of neuronal diseases, including epilepsy, schizophrenia, learning and attention deficit and drug addiction, and they are the targets for muscle relaxants, Alzheimer's drugs, anti-convulsants, tranquilizers, smoking cessation agents and anti-emetics; understanding the relationship between structure and function in these proteins is therefore of immense importance not only for understanding neurotransmission, but also for the development of novel therapeutic agents. The structures of many of these proteins have been revealed in the last few years, but molecular details of how these relate to function is still unclear. Our aim is to fully understand these.

Research objectives

  • What are the relationships between structure and function in the pLGIC family?

Key publications

Mosesso R, Dougherty DA, Lummis SCR (2019). Proline residues in the transmembrane/ extracellular domain interface loops have different behaviors in 5-HT3 and nACh receptors. ACS Chem. Neurosci., 10(7):3327-3333. doi: 10.1021/acschemneuro.9b00315

Mesoy S, Jeffreys J, Lummis SCR (2019). Characterization of residues in the 5-HT3 receptor M4 region that contribute to function. ACS Chem. Neurosci., 10(7):3167-3172. doi: 10.1021/acschemneuro.8b00603

Tang B, Lummis SCR (2018). Multiple regions in the extracellular domain of the glycine receptor determine receptor activity. J. Biol. Chem., 293(36):13889-13896. doi: 10.1074/jbc.RA118.003088

Price KL, Lummis SC (2014). An atypical residue in the pore of Varroa destructor GABA-activated RDL receptors affects picrotoxin block and thymol modulation. Insect Biochem. Mol. Biol., 55(1):19-25. doi: 10.1016/j.ibmb.2014.10.002

Ulens C, Spurny R, Thompson AJ, Alqazzaz M, Debaveye S, Han L, Price K, Villalgordo JM, Tresadern G, Lynch JW, Lummis SC (2014). The prokaryote ligand-gated ion channel ELIC captured in a pore blocker-bound conformation by the Alzheimer's disease drug memantine. Structure, 22(10):1399-1407. doi: 10.1016/j.str.2014.07.013