8ugs - Revision history

OCA at 08:24, 7 February 2024

OCA — Wed, 07 Feb 2024 08:24:18 GMT

←Older revision		Revision as of 08:24, 7 February 2024
Line 10:		Line 10:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/PDE6A_BOVIN PDE6A_BOVIN] This protein participates in processes of transmission and amplification of the visual signal.		[https://www.uniprot.org/uniprot/PDE6A_BOVIN PDE6A_BOVIN] This protein participates in processes of transmission and amplification of the visual signal.
-	<div style="background-color:#fffaf0;">
-	== 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<ref>PMID:38159849</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 8ugs" style="background-color:#fffaf0;"></div>
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 10:10, 17 January 2024

OCA — Wed, 17 Jan 2024 10:10:41 GMT

←Older revision		Revision as of 10:10, 17 January 2024
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 8ugs is ~~ON HOLD until Paper~~ Publication	+	==Cryo-EM structure of bovine phosphodiesterase 6 bound to cGMP==
		+	<StructureSection load='8ugs' size='340' side='right'caption='[[8ugs]], [[Resolution\|resolution]] 3.20Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8ugs]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8UGS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8UGS FirstGlance]. <br>
		+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 3.2Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PCG:CYCLIC+GUANOSINE+MONOPHOSPHATE'>PCG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8ugs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ugs OCA], [https://pdbe.org/8ugs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ugs RCSB], [https://www.ebi.ac.uk/pdbsum/8ugs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ugs ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/PDE6A_BOVIN PDE6A_BOVIN] This protein participates in processes of transmission and amplification of the visual signal.
		+	<div style="background-color:#fffaf0;">
		+	== 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.

-	~~Authors~~:	+	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<ref>PMID:38159849</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 8ugs" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Bos taurus]]
		+	[[Category: Large Structures]]
		+	[[Category: Aplin C]]
		+	[[Category: Cerione RA]]

OCA: Protected "8ugs" [edit=sysop:move=sysop]

OCA — Wed, 18 Oct 2023 12:25:20 GMT

Protected "8ugs" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:25, 18 October 2023

OCA: New page: '''Unreleased structure''' The entry 8ugs is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

OCA — Wed, 18 Oct 2023 12:25:17 GMT

New page: '''Unreleased structure''' The entry 8ugs is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8ugs is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]