- Tytuł:
- Ultrafast structural changes direct the first molecular events of vision
- Autorzy:
-
Mühle, Jonas
Kabanova, Victoria
Tsai, Ching-Ju
Cirelli, Claudio
Skopintsev, Petr
James, Daniel
Sen, Saumik
Diethelm, Azeglio D.
Deupi, Xavier
Panneels, Valerie
Martiel, Isabelle
Iwata, So
Milne, Christopher J.
Wach, Anna
Guixà-González, Ramon
Kekilli, Demet
Glover, Hannah
Knopp, Gregor
Brünle, Steffen
Mous, Sandra
Boutet, Sébastien
Standfuss, Jörg
Tanaka, Rie
Ortolani, Giorgia
Sarabi, Daniel
Gotthard, Guillaume
Joti, Yasumasa
Johnson, Philip J. M.
Tono, Kensuke
Rodrigues, Matthew J.
Casadei, Cecilia M.
Båth, Petra
Furrer, Antonia
Nogły, Przemysław
Weinert, Tobias
Neutze, Richard
Nango, Eriko
Varma, Niranjan
Schertler, Gebhard
Ma, Pikyee
Bacellar, Camila
Nass, Karol
Gruhl, Thomas
Lesca, Elena
Tejero, Oliver
Dworkowski, Florian
Ozerov, Dmitry
Owada, Shigeki
Pamula, Filip
Gashi, Dardan - Opis:
- Vision 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 temperature 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.
- Dostawca treści:
- Repozytorium Uniwersytetu Jagiellońskiego
Artykuł