Functional Cycle

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Hideki Kandori - One of the best experts on this subject based on the ideXlab platform.

  • Biophysics of rhodopsins and optogenetics
    Biophysical Reviews, 2020
    Co-Authors: Hideki Kandori
    Abstract:

    Rhodopsins are photoreceptive proteins and key tools in optogenetics. Although rhodopsin was originally named as a red-colored pigment for vision, the modern meaning of rhodopsin encompasses photoactive proteins containing a retinal chromophore in animals and microbes. Animal and microbial rhodopsins respectively possess 11- cis and all- trans retinal, respectively. As cofactors bound with their animal and microbial rhodopsin (seven transmembrane α-helices) environments, 11- cis and all- trans retinal undergo photoisomerization into all- trans and 13- cis retinal forms as part of their Functional Cycle. While animal rhodopsins are G protein coupled receptors, the function of microbial rhodopsins is highly divergent. Many of the microbial rhodopsins are able to transport ions in a passive or an active manner. These light-gated channels or light-driven pumps represent the main tools for respectively effecting neural excitation and silencing in the emerging field of optogenetics. In this article, the biophysics of rhodopsins and their relationship to optogenetics are reviewed. As history has proven, understanding the molecular mechanism of microbial rhodopsins is a prerequisite for their rational exploitation as the optogenetics tools of the future.

  • photochromism of anabaena sensory rhodopsin
    Journal of the American Chemical Society, 2007
    Co-Authors: Akira Kawanabe, Yuji Furutani, Kwang-hwan Jung, Hideki Kandori
    Abstract:

    Protein-controlled photochemical reactions often mediate biological light-signal and light-energy conversions. Microbial rhodopsins possess all-trans or 13-cis retinal as the chromophore in the dark, and in the light-driven proton pump, bacteriorhodopsin (BR), the stable photoproduct at the end of the Functional Cycle of the all-trans form is 100% all-trans. In contrast, a microbial rhodopsin discovered in Anabaena PCC7120 is believed to function as a photochromic sensor. For Anabaena sensory rhodopsin (ASR), the photoreaction is expected to be not cyclic, but photochromic. The present low-temperature UV−visible spectroscopy of ASR indeed revealed that the stable photoproduct of the all-trans form in ASR is 100% 13-cis, and that of the 13-cis form is 100% all-trans. The complete photoCycle for the proton pump in BR and the complete photochromism for the chromatic sensor of ASR are highly advantageous for their functions. Thus, the microbial rhodopsins have acquired unique photoreactions, in spite of their...

  • Photochromism of Anabaena sensory rhodopsin.
    Journal of the American Chemical Society, 2007
    Co-Authors: Akira Kawanabe, Yuji Furutani, Kwang-hwan Jung, Hideki Kandori
    Abstract:

    Protein-controlled photochemical reactions often mediate biological light-signal and light-energy conversions. Microbial rhodopsins possess all-trans or 13-cis retinal as the chromophore in the dark, and in the light-driven proton pump, bacteriorhodopsin (BR), the stable photoproduct at the end of the Functional Cycle of the all-trans form is 100% all-trans. In contrast, a microbial rhodopsin discovered in Anabaena PCC7120 is believed to function as a photochromic sensor. For Anabaena sensory rhodopsin (ASR), the photoreaction is expected to be not cyclic, but photochromic. The present low-temperature UV-visible spectroscopy of ASR indeed revealed that the stable photoproduct of the all-trans form in ASR is 100% 13-cis, and that of the 13-cis form is 100% all-trans. The complete photoCycle for the proton pump in BR and the complete photochromism for the chromatic sensor of ASR are highly advantageous for their functions. Thus, the microbial rhodopsins have acquired unique photoreactions, in spite of their similar structures, during evolution.

Sophie Lotersztajn - One of the best experts on this subject based on the ideXlab platform.

Assia Shisheva - One of the best experts on this subject based on the ideXlab platform.

  • active vacuolar h atpase and Functional Cycle of rab5 are required for the vacuolation defect triggered by ptdins 3 5 p2 loss under pikfyve or vps34 deficiency
    American Journal of Physiology-cell Physiology, 2016
    Co-Authors: Lauren M Compton, Ognian C Ikonomov, Diego Sbrissa, Puneet Garg, Assia Shisheva
    Abstract:

    The two evolutionarily conserved mammalian lipid kinases Vps34 and PIKfyve are involved in an important physiological relationship, whereby the former produces phosphatidylinositol (PtdIns) 3P that is used as a substrate for PtdIns(3,5)P2 synthesis by the latter. Reduced production of PtdIns(3,5)P2 in proliferating mammalian cells is phenotypically manifested by the formation of multiple translucent cytoplasmic vacuoles, readily rescued upon exogenous delivery of PtdIns(3,5)P2 or overproduction of PIKfyve. Although the aberrant vacuolation phenomenon has been frequently used as a sensitive Functional measure of localized PtdIns(3,5)P2 reduction, cellular factors governing the appearance of cytoplasmic vacuoles under PtdIns3P-PtdIns(3,5)P2 loss remain elusive. To gain further mechanistic insight about the vacuolation process following PtdIns(3,5)P2 reduction, in this study we sought for cellular mechanisms required for manifestation of the aberrant endomembrane vacuoles triggered by PIKfyve or Vps34 dysfunction. The latter was achieved by various means such as pharmacological inhibition, gene disruption, or dominant-interference in several proliferating mammalian cell types. We report here that inhibition of V-ATPase with bafilomycin A1 as well as inactivation of the GTP-GDP Cycle of Rab5a GTPase phenotypically rescued or completely precluded the cytoplasmic vacuolization despite the continued presence of inactivated PIKfyve or Vps34. Bafilomycin A1 also restored the aberrant EEA1-positive endosomes, enlarged upon short PIKfyve inhibition with YM201636. Together, our work identifies for the first time that factors such as active V-ATPase or Functional Rab5a Cycle are acting coincidentally with the PtdIns(3,5)P2 reduction in triggering formation of aberrant cytoplasmic vacuoles under PIKfyve or Vps34 dysfunction.

  • General role of GDP dissociation inhibitor 2 in membrane release of Rab proteins: modulations of its Functional interactions by in vitro and in vivo structural modifications.
    Biochemistry, 1999
    Co-Authors: Assia Shisheva, Sreenivasa R. Chinni, Carmen Demarco
    Abstract:

    The GDP dissociation inhibitors (GDIs) represent an important class of regulatory proteins in the Functional Cycle and recycling of Rab GTPases. Previous studies have demonstrated that GDI-1 can op...

Hansjoachim Wieden - One of the best experts on this subject based on the ideXlab platform.

  • elongation factor tu s nucleotide binding is governed by a thermodynamic landscape unique among bacterial translation factors
    Journal of the American Chemical Society, 2019
    Co-Authors: Dylan Girodat, Evan Mercier, Katherine E Gzyl, Hansjoachim Wieden
    Abstract:

    Molecular switches such as GTPases are powerful devices turning “on” or “off” biomolecular processes at the core of critical biological pathways. To develop molecular switches de novo, an intimate understanding of how they function is required. Here we investigate the thermodynamic parameters that define the nucleotide-dependent switch mechanism of elongation factor (EF) Tu as a prototypical molecular switch. EF-Tu alternates between GTP- and GDP-bound conformations during its Functional Cycle, representing the “on” and “off” states, respectively. We report for the first time that the activation barriers for nucleotide association are the same for both nucleotides, suggesting a guanosine nucleoside or ribose-first mechanism for nucleotide association. Additionally, molecular dynamics (MD) simulations indicate that enthalpic stabilization of GDP binding compared to GTP binding originates in the backbone hydrogen bonding network of EF-Tu. In contrast, binding of GTP to EF-Tu is entropically driven by the li...

Loredana Saveanu - One of the best experts on this subject based on the ideXlab platform.