Supplementary material from "It takes two transducins to activate the cGMP-phosphodiesterase 6 in retinal rods"

  • Bilal M. Qureshi (Creator)
  • Elmar Behrmann (Creator)
  • Johannes Schöneberg (Creator)
  • Justus Loerke (Creator)
  • Jörg Bürger (Creator)
  • Thorsten Mielke (Creator)
  • Jan Giesebrecht (Creator)
  • Frank Noé (Creator)
  • Trevor D. Lamb (Creator)
  • Klaus Peter Hofmann (Creator)
  • Christian M. T. Spahn (Creator)
  • Martin Heck (Creator)
  • Bilal M. Qureshi (Creator)
  • Elmar Behrmann (Creator)
  • Johannes Schöneberg (Creator)
  • Justus Loerke (Creator)
  • Jörg Bürger (Creator)
  • Thorsten Mielke (Creator)
  • Jan Giesebrecht (Creator)
  • Frank Noé (Creator)
  • Trevor D. Lamb (Creator)
  • Klaus Peter Hofmann (Creator)
  • Christian M. T. Spahn (Creator)
  • Martin Heck (Creator)

    Dataset

    Description

    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.
    Date made available2018
    Publisherfigshare
    • 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., Giesebrecht, J., Noé, F., Lamb, T. D., Hofmann, K. P., Spahn, C. M. T. & Heck, M., Aug 2018, In: Open Biology. 8, 8, p. 180075

      Research output: Contribution to journalArticlepeer-review

      21 Scopus citations

    Cite this