Ligand Binding Mechanisms in Human Cone Visual Pigments

Srinivasan, Sundaramoorthy; Guixà-González, Ramón; Cordomí, Arnau; Garriga, Pere

doi:10.1016/j.tibs.2019.02.001

Cited by 10 publications

(17 citation statements)

References 85 publications

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confidence: 95%

“…Moreover, because our proposed pathway would lead to breaking of the β-ionone ring, our study could stimulate further efforts in elucidating the retinal regeneration process, still largely under debate. 83 The importance of the Ce6 driven activation of RET is not only related to vision because similar mechanisms can take place in channelrhodopsin or rhodopsins that are not involved in vision. In the former, case the optimization of sensitizers may lead to the development of optogenetic cofactors allowing displacing the excitation wavelength toward the red, thus facilitating the possible implementation of optogenetic therapies in humans.…”

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confidence: 99%

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Induced Night Vision by Singlet-Oxygen-Mediated Activation of Rhodopsin

Marazzi

Gattuso

Giussani

et al. 2019

J. Phys. Chem. Lett.

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In humans, vision is limited to a small fraction of the whole electromagnetic spectrum. One possible strategy for enhancing vision in deep-red or poor-light conditions consists of recruiting chlorophyll derivatives in the rod photoreceptor cells of the eye, as suggested in the case of some deep-sea fish. Here, we employ all-atom molecular simulations and high-level quantum chemistry calculations to rationalize how chlorin e6 (Ce6), widely used in photodynamic therapy although accompanied by enhanced visual sensitivity, mediates vision in the dark, shining light on a fascinating but largely unknown molecular mechanism. First, we identify persistent interaction sites between Ce6 and the extracellular loops of rhodopsin, the transmembrane photoreceptor protein responsible for the first steps in vision. Triggered by Ce6 deep-red light absorption, the retinal within rhodopsin can be isomerized thus starting the visual phototransduction cascade. Our data largely exclude previously hypothesized energy-transfer mechanisms while clearly lending credence to a retinal isomerization indirectly triggered by singlet oxygen, proposing an alternative mechanism to rationalize photosensitizermediated night vision.

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confidence: 95%

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confidence: 99%

Induced Night Vision by Singlet-Oxygen-Mediated Activation of Rhodopsin

Marazzi

Gattuso

Giussani

et al. 2019

J. Phys. Chem. Lett.

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“…Here, we focus on the receptor–ligand sensing apparatus of cell, where complexes are formed at the cell membrane and subsequently internalized via endocytosis [ 31 ]. This sort of sensing mechanism is also relevant in the case of photoreceptors [ 57 ]. Receptors act as sensors for specific microenvironmental molecules (ligands) that bind together with a certain affinity to form complexes.…”

Section: Minimal Cell Sensing Noise Is Associated With Differentiated Tissue Spatial Configurationmentioning

confidence: 99%

Close to Optimal Cell Sensing Ensures the Robustness of Tissue Differentiation Process: The Avian Photoreceptor Mosaic Case

Barua

Beygi

Hatzikirou

2021

Entropy

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The way that progenitor cell fate decisions and the associated environmental sensing are regulated to ensure the robustness of the spatial and temporal order in which cells are generated towards a fully differentiating tissue still remains elusive. Here, we investigate how cells regulate their sensing intensity and radius to guarantee the required thermodynamic robustness of a differentiated tissue. In particular, we are interested in finding the conditions where dedifferentiation at cell level is possible (microscopic reversibility), but tissue maintains its spatial order and differentiation integrity (macroscopic irreversibility). In order to tackle this, we exploit the recently postulated Least microEnvironmental Uncertainty Principle (LEUP) to develop a theory of stochastic thermodynamics for cell differentiation. To assess the predictive and explanatory power of our theory, we challenge it against the avian photoreceptor mosaic data. By calibrating a single parameter, the LEUP can predict the cone color spatial distribution in the avian retina and, at the same time, suggest that such a spatial pattern is associated with quasi-optimal cell sensing. By means of the stochastic thermodynamics formalism, we find out that thermodynamic robustness of differentiated tissues depends on cell metabolism and cell sensing properties. In turn, we calculate the limits of the cell sensing radius that ensure the robustness of differentiated tissue spatial order. Finally, we further constrain our model predictions to the avian photoreceptor mosaic.

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“…Here, we focus on the receptor-ligand sensing apparatus of cell, where complexes are formed at cell membrane and subsequently internalized via endocytosis [31]. This sort of sensing mechanism is also relevant in the case of photoreceptors [57]. Receptors act as sensors for specific microenvironmental molecules (ligands) that bind together with a certain affinity to form complexes.…”

Section: Minimal Cell Sensing Noise Is Associated With Differentiated Tissue Spatial Configurationmentioning

confidence: 99%

Close to optimal cell sensing ensures the robustness of tissue differentiation process: the avian photoreceptor mosaic case

Barua

Beygi

Hatzikirou

2021

Preprint

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The way that progenitor cell fate decisions and the associated environmental sensing are regulated to ensure the robustness of the spatial and temporal order in which cells are generated towards a fully differentiating tissue still remains elusive. Here, we investigate how cells regulate their sensing intensity and radius to guarantee the required thermodynamic robustness of a differentiated tissue. In particular, we are interested in finding the conditions where dedifferentiation at cell level is possible (microscopic reversibility) but tissue maintains its spatial order and differentiation integrity (macroscopic irreversibility). In order to tackle this, we exploit the recently postulated Least microEnvironmental Uncertainty Principle (LEUP) to develop a theory of stochastic thermodynamics for cell differentiation. To assess the predictive and explanatory power of our theory, we challenge it against the avian photoreceptor mosaic data. By calibrating a single parameter, the LEUP can predict the cone color spatial distribution in the avian retina and, at the same time, suggest that such a spatial pattern is associated with quasi-optimal cell sensing. By means of the stochastic thermodynamics formalism, we find out that thermodynamic robustness of differentiated tissues depends on cell metabolism and cell sensing properties. In turn, we calculate the limits of the cell sensing radius that ensure the robustness of differentiated tissue spatial order. Finally, we further constrain our model predictions to the avian photoreceptor mosaic.

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Ligand Binding Mechanisms in Human Cone Visual Pigments

Abstract: Portal del coneixement obert de la UPC http://upcommons.upc.edu/e-prints Aquesta és una còpia de la versió author's final draft d'un article publicat a la revista Trends in biochemical sciences.

Cited by 10 publications

References 85 publications

Induced Night Vision by Singlet-Oxygen-Mediated Activation of Rhodopsin

Induced Night Vision by Singlet-Oxygen-Mediated Activation of Rhodopsin

Close to Optimal Cell Sensing Ensures the Robustness of Tissue Differentiation Process: The Avian Photoreceptor Mosaic Case

Close to optimal cell sensing ensures the robustness of tissue differentiation process: the avian photoreceptor mosaic case

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