Light-Sensitive Membrane Proteins as Tools to Generate Precision Treatments

J Membr Biol. 2020 Apr;253(2):81-86. doi: 10.1007/s00232-020-00115-4. Epub 2020 Apr 4.

Abstract

INTRODUCTION BY ANA-NICOLETA BONDAR, BIOPHYSICS SECTION HEAD EDITOR: This issue of the Journal of Membrane Biology inaugurates Up-and-Coming Scientist, in which investigators at early career stages are invited to present recent research in the broad context of their discipline. We inaugurate Up-and-Coming Scientist with the essay by Dr. Elena Lesca of the ETH Zürich and the Paul Scherrer Institut, Switzerland. Dr. Lesca has completed her doctoral degree at the Technical University München, Germany, in 2014, and pursued postdoctoral research at the ETH Zürich and Paul Scherrer Institut, where she is Senior Assistant since 2019. Two recent papers by Dr. Lesca et al. (references 33 and 39) have used X-ray crystallography and experimental biophysics approaches to shed light on the mechanism of action of a membrane receptor from the G Protein-Coupled Receptor (GPCR) family, Jumping Spider Rhodopsin-1 (JSR-1). JSR-1 is a visual rhodopsin activated upon absorption of light by its covalently bound retinal chromophore. Unlike the better-understood bovine rhodopsin GPCR, which is monostable, JSR-1 is bistable (i.e., in JSR-1 the Schiff base that binds retinal to the protein stays protonated throughout the reaction cycle), and absorption of a second photon resets the retinal ligand to the resting state configuration. In her essay, Dr. Lesca discusses the implications of her work on JSR-1 and, more broadly, GPCR research, for state-of-the-art applications in optogenetics and drug design.

Keywords: GPCR; Optogenetics; Photopharmacology; Photoswitches; Rhodopsin.

Publication types

  • Biography
  • Historical Article
  • Letter

MeSH terms

  • Drug Discovery
  • History, 21st Century
  • Light*
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism*
  • Precision Medicine* / methods
  • Protein Binding / radiation effects
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / metabolism
  • Structure-Activity Relationship

Substances

  • Membrane Proteins
  • Receptors, G-Protein-Coupled