Higher-order architecture of rhodopsin in intact photoreceptors and its implication for phototransduction kinetics.
The visual pigment rhodopsin belongs to the family of G protein-coupled receptors that can form higher oligomers. It is controversial whether rhodopsin forms oligomers and whether oligomers are functionally relevant. Here, we study rhodopsin organization in cryosections of dark-adapted mouse rod photoreceptors by cryoelectron tomography. We identify four hierarchical levels of organization. Rhodopsin forms dimers; at least ten dimers form a row. Rows form pairs (tracks) that are aligned parallel to the disk incisures. Particle-based simulation shows that the combination of tracks with fast precomplex formation, i.e. rapid association and dissociation between inactive rhodopsin and the G protein transducin, leads to kinetic trapping: rhodopsin first activates transducin from its own track, whereas recruitment of transducin from other tracks proceeds more slowly. The trap mechanism could produce uniform single-photon responses independent of rhodopsin lifetime. In general, tracks might provide a platform that coordinates the spatiotemporal interaction of signaling molecules.
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research (caesar), Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.
Monika
M
Gunkel
Computational Molecular Biology Group, Freie Universität Berlin, Arnimallee 6, 14195 Berlin, Germany.
Johannes
J
Schöneberg
German Center of Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.
Weaam
W
Alkhaldi
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research (caesar), Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.
Stephan
S
Irsen
Computational Molecular Biology Group, Freie Universität Berlin, Arnimallee 6, 14195 Berlin, Germany.
Frank
F
Noé
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research (caesar), Ludwig-Erhard-Allee 2, 53175 Bonn, Germany. Electronic address: u.b.kaupp@caesar.de.
U Benjamin
UB
Kaupp
German Center of Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany. Electronic address: ashraf.al-amoudi@dzne.de.
Ashraf
A
Al-Amoudi
D000818:Animals; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D010786:Photoreceptor Cells / Q000378:metabolism / Q000648:ultrastructure*; D011485:Protein Binding; D055503:Protein Multimerization; D012243:Rhodopsin / Q000737:chemistry* / Q000378:metabolism; D015293:Transducin / Q000378:metabolism; D014785:Vision, Ocular
D012243:Rhodopsin; D015293:Transducin