Year: 2026
Type: preprint
Abstract: G-protein-coupled receptors of the Rhodopsin family are crucial medicinal targets, transmitting signals across biomembranes. While light absorption by visual rhodopsin is well studied, its activation via retinal cofactor dynamics remains unclear. Here we use a free-electron laser to show that time-resolved X-ray solution scattering captures the retinal cis–trans isomerization as it passes the conical intersection of excited and ground-state photoproduct energy surfaces. Femtosecond-scale nuclear changes occur due to resonant photon absorption, with all-atom simulations revealing ultrafast amino acid movements that initiate transmembrane helix shifts. Ligand-free opsin measurements confirm that light activation is unaffected by non-resonant processes, showing the photonic energy is directly transmitted within the protein. Our method unveils how cofactor dynamics activate rhodopsin, free of constraints from crystal lattice packing or cryotrapping photointermediates.
Authors: Thomas D. Grant, Suchithranga M.D.C. Perera, Leslie A. Salas-Estrada, C. Swathi K. Menon, Andrey V. Struts, Xiaolin Xu, Steven D. E. Fried, Nipuna Weerasinghe, Udeep Chawla, Roberto Alvarez, Hao Hu, Konstantinos Karpos, Stella Lisova, Reza Nazari, Sahba Zaare, Jesse Coe, Raimund Fromme, Domingo Meza, Abhishek Singharoy, Sarah R. Chamberlain, Stephen Moore, Nadia A. Zatsepin, Fivos Perakis, Sergio Carbajo, Mark S. Hunter, Mengning Liang, Matthew D. Seaberg, Sébastien Boutet, Derek Mendez, Alan Grossfield, Petra Fromme, Richard A. Kirian, Michael F. Brown
Institutions: University at Buffalo, State University of New York, University of Arizona, University of Rochester Medicine, University of Rochester, Arizona State University, Stockholm University, AlbaNova, California NanoSystems Institute, University of California, Los Angeles, SLAC National Accelerator Laboratory, Linac Coherent Light Source
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, U.S. Department of Energy, Arizona State University, University of Arizona, University of Rochester, Russian Foundation for Basic Research, Knut och Alice Wallenbergs Stiftelse, National Institutes of Health, Office of Science, National Eye Institute, National Institute of General Medical Sciences, Division of Chemistry, Basic Energy Sciences, SLAC National Accelerator Laboratory
Awards: G1019100964, G121915436, G1229526393, G1286251239, G1500833948, G1645119126, MEMBRANE BASIS OF VISUAL EXCITATION, Light-Induced Protein Quake of Visual Rhodopsin Investigated by Femtosecond Time-Resolved X-Ray Scattering, G2371548206, G2411683797, G2584197162, G262532246, G2988778103, G303061748, High-resolution molecular recognition of ligands using solution X-ray scattering, G3945850812, G4168648347, G4235786860, MEMBRANE BASIS OF VISUAL EXCITATION, G4654690619, G495301720, G498139845, G5563220810, G5570207115, CAREER: Imaging dynamic macromolecules in solution with x-ray lasers, G5986892838, G6550344761, G6671297155, G705923083, G7283024673, ABI Innovation: New Algorithms for Biological X-ray Free Electron Laser Data, G7904749588, Essential Role of Water and Lipids in G-Protein-Coupled Receptor Chemistry, G7938408761, G807938293, G8269158468, G8382000481, G8906985441, G8925327636, G911061179, Biology with X-ray Lasers, G969889393
OpenAlex ID: W7168923526