8ugb | pdb_00008ugb

Cryo-EM structure of bovine phosphodiesterase 6 bound to udenafil

spinqualitylabelsall models 8ugb, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8ugb is a 4 chain structure with sequence from Bos taurus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3Å Ligands: MG, PCG, ZN, ZUD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PDE6A_BOVIN This protein participates in processes of transmission and amplification of the visual signal. Publication Abstract from PubMed Phototransduction in retinal rods occurs when the G protein-coupled photoreceptor rhodopsin triggers the activation of phosphodiesterase 6 (PDE6) by GTP-bound alpha subunits of the G protein transducin (Galpha(T)). Recently, we presented a cryo-EM structure for a complex between 2 GTP-bound recombinant Galpha(T) subunits and native PDE6, that included a bivalent antibody bound to the C-terminal ends of Galpha(T) and the inhibitor vardenafil occupying the active sites on the PDEalpha and PDEbeta subunits. We proposed Galpha(T) activated PDE6 by inducing a striking reorientation of the PDEgamma subunits away from the catalytic sites. However, questions remained including whether in the absence of the antibody Galpha(T) binds to PDE6 in a similar manner as observed when the antibody is present, does Galpha(T) activate PDE6 by enabling the substrate cGMP to access the catalytic sites, and how does the lipid membrane enhance PDE6 activation? Here we demonstrate that 2:1 Galpha(T)-PDE6 complexes form with either recombinant or retinal Galpha(T) in the absence of the Galpha(T) antibody. We show that Galpha(T) binding is not necessary for cGMP nor competitive inhibitors to access the active sites; instead, occupancy of the substrate binding sites enables Galpha(T) to bind and reposition the PDE6gamma subunits to promote catalytic activity. Moreover, we demonstrate by reconstituting Galpha(T)-stimulated PDE6 activity in lipid bilayer nanodiscs that the membrane-induced enhancement results from an increase in the apparent binding affinity of Galpha(T) for PDE6. These findings provide new insights into how the retinal G protein stimulates rapid catalytic turnover by PDE6 required for dim light vision. Probing the mechanism by which the retinal G protein transducin activates its biological effector PDE6.,Aplin C, Cerione RA J Biol Chem. 2023 Dec 28:105608. doi: 10.1016/j.jbc.2023.105608. PMID:38159849 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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