Hosted by Anthony Fitzpatrick, PhD, on behalf of the Department of Biochemistry and Molecular Biophysics

Abstract:
The muscle-type nicotinic acetylcholine receptor (nAChR) is the archetypal ligand gated ion channel studied in multiple disciplines for more than a century.  It was the first ion channel identified, purified and imaged by electron microscopy and efforts to determine the atomic structure have been ongoing for more than 50 years. We describe our efforts towards elucidating the structure of the channel and the development of bespoke affinity ligands that facilitated the rapid purification and first high-resolution cryoEM structure of the native receptor. We further describe the structural details of the resting and desensitized states, lipid and cholesterol binding and modulation and proposed gating mechanisms. Finally, we describe the d-tubocurarine bound state and speculate on the potential for developing improved muscle relaxants and the development of time-resolved EM tools for capturing the open state of the receptor.

Bio:
Michael Stowell received his PhD in Chemistry and Biophysics from the California Institute of Technology and was a Postdoctoral Scientist at the MRC – Laboratory of Molecular Biology, Cambridge England and the Biophysics Department of Kyoto University, Japan. Dr. Stowell has authored publications in the fields of synthetic organic chemistry, mechanical engineering, structural biology, neurobiology, and biophysics and uses cryo-EM and cryo-ET to investigate synaptic proteins and synaptic architecture. He is currently a professor in the department of Molecular, Cellular and Developmental Biology at CU Boulder, the Faculty Director of the CU Boulder EM Services Core, and a co-director of the NIH Funded CU Boulder Center for Cryo-ET (CCET).