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  It takes two transducins to activate the cGMP-phosphodiesterase 6 in retinal rods

Qureshi, B. M., Behrmann, E., Schöneberg, J., Loerke, J., Bürger, J., Mielke, T., et al. (2018). It takes two transducins to activate the cGMP-phosphodiesterase 6 in retinal rods. Open Biology, 8(8): 180075. doi:10.1098/rsob.180075.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0003-564C-8 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-5654-E
Genre: Journal Article

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 Creators:
Qureshi, Bilal M., Author
Behrmann, Elmar1, Author
Schöneberg, Johannes, Author
Loerke, Justus, Author
Bürger, Jörg2, Author              
Mielke, Thorsten2, Author              
Giesebrecht, Jan, Author
Noé, Frank , Author
Lamb, Trevor D., Author
Hofmann, Klaus Peter, Author
Spahn, Christian M. T., Author
Heck, Martin, Author
Affiliations:
1Max Planck Research Group Structural Dynamics of Proteins, Center of Advanced European Studies and Research (caesar), Max Planck Society, Ludwig-Erhard-Allee 2, 53175 Bonn, DE, ou_2173687              
2Microscopy and Cryo-Electron Microscopy (Head: Thorsten Mielke), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479668              

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Free keywords: PDE6; coincidence switch; density switch; noise filtering; visual signal transduction
 Abstract: Among cyclic nucleotide phosphodiesterases (PDEs), PDE6 is unique in serving as an effector enzyme in G protein-coupled signal transduction. In retinal rods and cones, PDE6 is membrane-bound and activated to hydrolyse its substrate, cGMP, by binding of two active G protein α-subunits (Gα*). To investigate the activation mechanism of mammalian rod PDE6, we have collected functional and structural data, and analysed them by reaction-diffusion simulations. Gα* titration of membrane-bound PDE6 reveals a strong functional asymmetry of the enzyme with respect to the affinity of Gα* for its two binding sites on membrane-bound PDE6 and the enzymatic activity of the intermediary 1 : 1 Gα* · PDE6 complex. Employing cGMP and its 8-bromo analogue as substrates, we find that Gα* · PDE6 forms with high affinity but has virtually no cGMP hydrolytic activity. To fully activate PDE6, it takes a second copy of Gα* which binds with lower affinity, forming Gα* · PDE6 · Gα*. Reaction-diffusion simulations show that the functional asymmetry of membrane-bound PDE6 constitutes a coincidence switch and explains the lack of G protein-related noise in visual signal transduction. The high local concentration of Gα* generated by a light-activated rhodopsin molecule efficiently activates PDE6, whereas the low density of spontaneously activated Gα* fails to activate the effector enzyme.

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Language(s): eng - English
 Dates: 2018-07-062018-08-01
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: ISI: 000443334800004
DOI: 10.1098/rsob.180075
 Degree: -

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Title: Open Biology
  Abbreviation : Open Biol
Source Genre: Journal
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Publ. Info: Royal Society
Pages: - Volume / Issue: 8 (8) Sequence Number: 180075 Start / End Page: - Identifier: Other: 2630944-0
Other: 2046-2441
CoNE: https://pure.mpg.de/cone/journals/resource/2046-2441