Molecules (Sep 2021)

Pursuing High-Resolution Structures of Nicotinic Acetylcholine Receptors: Lessons Learned from Five Decades

  • Manuel Delgado-Vélez,
  • Orestes Quesada,
  • Juan C. Villalobos-Santos,
  • Rafael Maldonado-Hernández,
  • Guillermo Asmar-Rovira,
  • Raymond C. Stevens,
  • José Antonio Lasalde-Dominicci

DOI
https://doi.org/10.3390/molecules26195753
Journal volume & issue
Vol. 26, no. 19
p. 5753

Abstract

Read online

Since their discovery, nicotinic acetylcholine receptors (nAChRs) have been extensively studied to understand their function, as well as the consequence of alterations leading to disease states. Importantly, these receptors represent pharmacological targets to treat a number of neurological and neurodegenerative disorders. Nevertheless, their therapeutic value has been limited by the absence of high-resolution structures that allow for the design of more specific and effective drugs. This article offers a comprehensive review of five decades of research pursuing high-resolution structures of nAChRs. We provide a historical perspective, from initial structural studies to the most recent X-ray and cryogenic electron microscopy (Cryo-EM) nAChR structures. We also discuss the most relevant structural features that emerged from these studies, as well as perspectives in the field.

Keywords