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Cryo-EM studies of nicotinic acetylcholine receptors


EMSL Project ID
50839

Abstract

Nicotinic acetylcholine receptors mediate fast chemical neurotransmission throughout the central and peripheral nervous systems. Nicotinic receptors in the brain are the first point of action contributing to the stimulant and addictive properties of nicotine. The nicotinic receptor at the neuromuscular junction mediates the fast communication between motor neurons and the endplate on muscle fibers. My lab is engaged in a long term structural biology research effort on distinct subtypes and ligand complexes of nicotinic acetylcholine receptors. We now have several projects at different stages of development. We propose four aims, each focused on a distinct receptor subunit assembly. Strong biochemistry and in some cases new mid to high resolution reconstructions support feasibility of each aim. Our overall goals are to provide a robust structural foundation for understanding allosteric gating, subunit assembly, ion permeation, interactions with lipids, and ligand recognition and selectivity between distinct receptor types.

Project Details

Start Date
2019-04-15
End Date
2021-03-17
Status
Closed

Team

Principal Investigator

Ryan Hibbs
Institution
University of Texas Southwestern Medical Center

Team Members

Umang Goswami
Institution
University of Texas Southwestern Medical Center

MD Rahman
Institution
University of Texas Southwestern Medical Center

Guipeun Kang
Institution
University of Texas Southwestern Medical Center

Colleen Noviello
Institution
University of Texas Southwestern Medical Center

Harry Scott
Institution
Oregon Health & Science University

Related Publications

Leah Baxter, Dominika Borek, Rico Cabuco, Anant Gharpure, Ryan E. Hibbs, Nuriya Mukhtasimova, Colleen M. Noviello, Steven M. Sine. 2021. "Structure and gating mechanism of the α7 nicotinic acetylcholine receptor." Cell 10.1016/j.cell.2021.02.049
Structure of the Native Muscle-type Nicotinic Receptor and Inhibition by Snake Venom Toxins. Rahman MM, Teng J, Worrell BT, Noviello CM, Lee M, Karlin A, Stowell MHB, Hibbs RE. Neuron. 2020 Apr 2. pii: S0896-6273(20)30219-1. doi: 10.1016/j.neuron.2020.03.012. [Epub ahead of print] PMID: 32275860