Ultrafast structural changes direct the first molecular events of vision
Author:
Gruhl ThomasORCID, Weinert TobiasORCID, Rodrigues Matthew J.ORCID, Milne Christopher J.ORCID, Ortolani GiorgiaORCID, Nass Karol, Nango Eriko, Sen SaumikORCID, Johnson Philip J. M.ORCID, Cirelli ClaudioORCID, Furrer AntoniaORCID, Mous SandraORCID, Skopintsev PetrORCID, James DanielORCID, Dworkowski FlorianORCID, Båth PetraORCID, Kekilli DemetORCID, Ozerov DmitryORCID, Tanaka RieORCID, Glover HannahORCID, Bacellar CamilaORCID, Brünle Steffen, Casadei Cecilia M.ORCID, Diethelm Azeglio D.ORCID, Gashi Dardan, Gotthard GuillaumeORCID, Guixà-González RamonORCID, Joti YasumasaORCID, Kabanova Victoria, Knopp GregorORCID, Lesca Elena, Ma Pikyee, Martiel Isabelle, Mühle JonasORCID, Owada Shigeki, Pamula Filip, Sarabi Daniel, Tejero OliverORCID, Tsai Ching-JuORCID, Varma Niranjan, Wach AnnaORCID, Boutet SébastienORCID, Tono KensukeORCID, Nogly PrzemyslawORCID, Deupi XavierORCID, Iwata So, Neutze RichardORCID, Standfuss JörgORCID, Schertler GebhardORCID, Panneels ValerieORCID
Abstract
AbstractVision is initiated by the rhodopsin family of light-sensitive G protein-coupled receptors (GPCRs)1. A photon is absorbed by the 11-cis retinal chromophore of rhodopsin, which isomerizes within 200 femtoseconds to the all-trans conformation2, thereby initiating the cellular signal transduction processes that ultimately lead to vision. However, the intramolecular mechanism by which the photoactivated retinal induces the activation events inside rhodopsin remains experimentally unclear. Here we use ultrafast time-resolved crystallography at room temperature3 to determine how an isomerized twisted all-trans retinal stores the photon energy that is required to initiate the protein conformational changes associated with the formation of the G protein-binding signalling state. The distorted retinal at a 1-ps time delay after photoactivation has pulled away from half of its numerous interactions with its binding pocket, and the excess of the photon energy is released through an anisotropic protein breathing motion in the direction of the extracellular space. Notably, the very early structural motions in the protein side chains of rhodopsin appear in regions that are involved in later stages of the conserved class A GPCR activation mechanism. Our study sheds light on the earliest stages of vision in vertebrates and points to fundamental aspects of the molecular mechanisms of agonist-mediated GPCR activation.
Publisher
Springer Science and Business Media LLC
Subject
Multidisciplinary
Reference105 articles.
1. Hofmann, K. P. et al. A G protein-coupled receptor at work: the rhodopsin model. Trends Biochem. Sci. 34, 540–552 (2009). 2. Schoenlein, R. W., Peteanu, L. A., Mathies, R. A. & Shank, C. V. The first step in vision: femtosecond isomerization of rhodopsin. Science 254, 412–415 (1991). 3. Branden, G. & Neutze, R. Advances and challenges in time-resolved macromolecular crystallography. Science 373, eaba0954 (2021). 4. Sakmar, T. P., Franke, R. R. & Khorana, H. G. Glutamic acid-113 serves as the retinylidene Schiff base counterion in bovine rhodopsin. Proc. Natl Acad. Sci. USA 86, 8309–8313 (1989). 5. Palczewski, K. et al. Crystal structure of rhodopsin: a G protein-coupled receptor. Science 289, 739–745 (2000).
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