8dvs - Revision history

OCA at 09:01, 4 June 2025

2025-06-04T09:01:50Z

← Older revision		Revision as of 09:01, 4 June 2025
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	RIG-I is an essential innate immune receptor for detecting and responding to infection by RNA viruses. RIG-I specifically recognizes the unique molecular features of viral RNA molecules and selectively distinguishes them from closely related RNAs abundant in host cells. The physical basis for this exquisite selectivity is revealed through a series of high-resolution cryo-EM structures of RIG-I in complex with host and viral RNA ligands. These studies demonstrate that RIG-I actively samples double-stranded RNAs in the cytoplasm and distinguishes them by adopting two different types of protein folds. Upon binding viral RNA, RIG-I adopts a high-affinity conformation that is conducive to signaling, while host RNA induces an autoinhibited conformation that stimulates RNA release. By coupling protein folding with RNA binding selectivity, RIG-I distinguishes RNA molecules that differ by as little as one phosphate group, thereby explaining the molecular basis for selective antiviral sensing and the induction of autoimmunity upon RIG-I dysregulation.		RIG-I is an essential innate immune receptor for detecting and responding to infection by RNA viruses. RIG-I specifically recognizes the unique molecular features of viral RNA molecules and selectively distinguishes them from closely related RNAs abundant in host cells. The physical basis for this exquisite selectivity is revealed through a series of high-resolution cryo-EM structures of RIG-I in complex with host and viral RNA ligands. These studies demonstrate that RIG-I actively samples double-stranded RNAs in the cytoplasm and distinguishes them by adopting two different types of protein folds. Upon binding viral RNA, RIG-I adopts a high-affinity conformation that is conducive to signaling, while host RNA induces an autoinhibited conformation that stimulates RNA release. By coupling protein folding with RNA binding selectivity, RIG-I distinguishes RNA molecules that differ by as little as one phosphate group, thereby explaining the molecular basis for selective antiviral sensing and the induction of autoimmunity upon RIG-I dysregulation.

	~~The RIG-I receptor adopts two different conformations for distinguishing host from viral RNA ligands.~~,~~Wang W, Pyle AM Mol Cell. 2022 Nov 3;82(21):4131-4144.e6. doi: 10.1016/j.molcel.2022.09.029. Epub , 2022 Oct 21.~~ PMID:36272408<ref>PMID:36272408</ref>		, PMID:36272408<ref>PMID:36272408</ref>

	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

OCA at 05:23, 12 June 2024

2024-06-12T05:23:11Z

← Older revision		Revision as of 05:23, 12 June 2024
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	==Cryo-EM structure of ~~protein~~-~~RNA complex 8~~==		==Cryo-EM structure of RIG-I bound to the end of OHSLR30 (+ATP)==
	<StructureSection load='8dvs' size='340' side='right'caption='[[8dvs]], [[Resolution\|resolution]] 3.00Å' scene=''>		<StructureSection load='8dvs' size='340' side='right'caption='[[8dvs]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[8dvs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DVS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DVS FirstGlance]. <br>		<table><tr><td colspan='2'>[[8dvs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DVS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DVS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 3Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=8dvs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dvs OCA], [https://pdbe.org/8dvs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dvs RCSB], [https://www.ebi.ac.uk/pdbsum/8dvs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dvs ProSAT]</span></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=8dvs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dvs OCA], [https://pdbe.org/8dvs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dvs RCSB], [https://www.ebi.ac.uk/pdbsum/8dvs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dvs ProSAT]</span></td></tr>
	</table>		</table>
			== Disease ==
			[https://www.uniprot.org/uniprot/RIGI_HUMAN RIGI_HUMAN] Singleton-Merten dysplasia. The disease is caused by variants affecting the gene represented in this entry.
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/~~DDX58_HUMAN DDX58_HUMAN~~] Innate immune receptor ~~which acts as a~~ cytoplasmic ~~sensor of~~ viral nucleic acids and ~~plays~~ a ~~major role~~ in ~~sensing viral infection~~ and in the ~~activation of a cascade~~ of antiviral ~~responses~~ including the ~~induction of type I~~ interferons ~~and proinflammatory cytokines~~. ~~Its ligands~~ include: 5'-triphosphorylated ~~ssRNA and dsRNA~~ and short ~~dsRNA~~ (<1 kb in length). In addition to the 5'-triphosphate moiety, blunt-end base pairing at the 5'-end of the RNA is very essential. Overhangs at the non-triphosphorylated end of the dsRNA RNA have no major impact on its activity. A 3'overhang at the 5'triphosphate end decreases and any 5'overhang at the 5' triphosphate end abolishes its activity~~. Upon ligand binding it associates with mitochondria antiviral signaling protein~~ (~~MAVS/IPS1) which activates the IKK-related kinases~~: ~~TBK1 and IKBKE which phosphorylate interferon regulatory factors~~: ~~IRF3 and IRF7 which in turn activate transcription of antiviral immunological genes~~, ~~including interferons (IFNs~~)~~; IFN-alpha and IFN-beta~~. Detects both positive and negative strand RNA viruses including members of the families Paramyxoviridae: Human respiratory syncytial virus and measles virus (MeV), Rhabdoviridae: vesicular stomatitis virus (VSV), Orthomyxoviridae: influenza A and B virus, Flaviviridae: Japanese encephalitis virus (JEV), hepatitis C virus (HCV), dengue virus (DENV) and west Nile virus (WNV). It also detects ~~rotavirus~~ and ~~reovirus~~. Also involved in antiviral signaling in response to viruses containing a dsDNA genome such as Epstein-Barr virus (EBV). Detects dsRNA produced from non-self dsDNA by RNA polymerase III, such as Epstein-Barr virus-encoded RNAs (EBERs). May play important roles in granulocyte production and differentiation, bacterial phagocytosis and in the regulation of cell migration.<ref>PMID:15208624</ref> <ref>PMID:16125763</ref> <ref>PMID:~~15708988~~</ref> <ref>PMID:16153868</ref> <ref>PMID:~~16127453~~</ref> <ref>PMID:~~17190814~~</ref> <ref>PMID:~~18636086~~</ref> <ref>PMID:19631370</ref> <ref>PMID:~~19576794~~</ref> <ref>PMID:~~19122199~~</ref> <ref>PMID:~~19211564~~</ref> <ref>PMID:~~19609254~~</ref> <ref>PMID:~~21742966~~</ref>		[https://www.uniprot.org/uniprot/RIGI_HUMAN RIGI_HUMAN] Innate immune receptor that senses cytoplasmic viral nucleic acids and activates a downstream signaling cascade leading to the production of type I interferons and pro-inflammatory cytokines (PubMed:15208624, PubMed:15708988, PubMed:16125763, PubMed:16127453, PubMed:16153868, PubMed:17190814, PubMed:18636086, PubMed:19122199, PubMed:19211564, PubMed:24366338, PubMed:28469175, PubMed:29117565, PubMed:31006531, PubMed:34935440, PubMed:35263596, PubMed:36793726). Forms a ribonucleoprotein complex with viral RNAs on which it homooligomerizes to form filaments (PubMed:15208624, PubMed:15708988). The homooligomerization allows the recruitment of RNF135 an E3 ubiquitin-protein ligase that activates and amplifies the RIG-I-mediated antiviral signaling in an RNA length-dependent manner through ubiquitination-dependent and -independent mechanisms (PubMed:28469175, PubMed:31006531). Upon activation, associates with mitochondria antiviral signaling protein (MAVS/IPS1) that activates the IKK-related kinases TBK1 and IKBKE which in turn phosphorylate the interferon regulatory factors IRF3 and IRF7, activating transcription of antiviral immunological genes including the IFN-alpha and IFN-beta interferons (PubMed:28469175, PubMed:31006531). Ligands include 5'-triphosphorylated ssRNAs and dsRNAs but also short dsRNAs (<1 kb in length) (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966). In addition to the 5'-triphosphate moiety, blunt-end base pairing at the 5'-end of the RNA is very essential (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966). Overhangs at the non-triphosphorylated end of the dsRNA RNA have no major impact on its activity (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966). A 3'overhang at the 5'triphosphate end decreases and any 5'overhang at the 5' triphosphate end abolishes its activity (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966). Detects both positive and negative strand RNA viruses including members of the families Paramyxoviridae: Human respiratory syncytial virus and measles virus (MeV), Rhabdoviridae: vesicular stomatitis virus (VSV), Orthomyxoviridae: influenza A and B virus, Flaviviridae: Japanese encephalitis virus (JEV), hepatitis C virus (HCV), dengue virus (DENV) and west Nile virus (WNV) (PubMed:21616437, PubMed:21884169). It also detects rotaviruses and reoviruses (PubMed:21616437, PubMed:21884169). Detects and binds to SARS-CoV-2 RNAs which is inhibited by m6A RNA modifications (Ref.70). Also involved in antiviral signaling in response to viruses containing a dsDNA genome such as Epstein-Barr virus (EBV) (PubMed:19631370). Detects dsRNA produced from non-self dsDNA by RNA polymerase III, such as Epstein-Barr virus-encoded RNAs (EBERs). May play important roles in granulocyte production and differentiation, bacterial phagocytosis and in the regulation of cell migration.<ref>PMID:15208624</ref> <ref>PMID:15708988</ref> <ref>PMID:16125763</ref> <ref>PMID:16127453</ref> <ref>PMID:16153868</ref> <ref>PMID:17190814</ref> <ref>PMID:18636086</ref> <ref>PMID:19122199</ref> <ref>PMID:19211564</ref> <ref>PMID:19576794</ref> <ref>PMID:19609254</ref> <ref>PMID:19631370</ref> <ref>PMID:21742966</ref> <ref>PMID:24366338</ref> <ref>PMID:28469175</ref> <ref>PMID:29117565</ref> <ref>PMID:31006531</ref> <ref>PMID:34935440</ref> <ref>PMID:35263596</ref> <ref>PMID:36793726</ref> [REFERENCE:70]<ref>PMID:21616437</ref> <ref>PMID:21884169</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
	RIG-I is an essential innate immune receptor for detecting and responding to infection by RNA viruses. RIG-I specifically recognizes the unique molecular features of viral RNA molecules and selectively distinguishes them from closely related RNAs abundant in host cells. The physical basis for this exquisite selectivity is revealed through a series of high-resolution cryo-EM structures of RIG-I in complex with host and viral RNA ligands. These studies demonstrate that RIG-I actively samples double-stranded RNAs in the cytoplasm and distinguishes them by adopting two different types of protein folds. Upon binding viral RNA, RIG-I adopts a high-affinity conformation that is conducive to signaling, while host RNA induces an autoinhibited conformation that stimulates RNA release. By coupling protein folding with RNA binding selectivity, RIG-I distinguishes RNA molecules that differ by as little as one phosphate group, thereby explaining the molecular basis for selective antiviral sensing and the induction of autoimmunity upon RIG-I dysregulation.		RIG-I is an essential innate immune receptor for detecting and responding to infection by RNA viruses. RIG-I specifically recognizes the unique molecular features of viral RNA molecules and selectively distinguishes them from closely related RNAs abundant in host cells. The physical basis for this exquisite selectivity is revealed through a series of high-resolution cryo-EM structures of RIG-I in complex with host and viral RNA ligands. These studies demonstrate that RIG-I actively samples double-stranded RNAs in the cytoplasm and distinguishes them by adopting two different types of protein folds. Upon binding viral RNA, RIG-I adopts a high-affinity conformation that is conducive to signaling, while host RNA induces an autoinhibited conformation that stimulates RNA release. By coupling protein folding with RNA binding selectivity, RIG-I distinguishes RNA molecules that differ by as little as one phosphate group, thereby explaining the molecular basis for selective antiviral sensing and the induction of autoimmunity upon RIG-I dysregulation.

	The RIG-I receptor adopts two different conformations for distinguishing host from viral RNA ligands.,Wang W, Pyle AM Mol Cell. 2022 ~~Oct 13. pii: S1097-2765~~(22)~~00950~~-9. doi:, 10.1016/j.molcel.2022.09.029. PMID:36272408<ref>PMID:36272408</ref>		The RIG-I receptor adopts two different conformations for distinguishing host from viral RNA ligands.,Wang W, Pyle AM Mol Cell. 2022 Nov 3;82(21):4131-4144.e6. doi: 10.1016/j.molcel.2022.09.029. Epub , 2022 Oct 21. PMID:36272408<ref>PMID:36272408</ref>

	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

OCA at 20:16, 16 November 2022

2022-11-16T20:16:39Z

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-The entry 8dvs is ON HOLD  until Paper Publication
+==Cryo-EM structure of protein-RNA complex 8==
-Authors:
+The RIG-I receptor adopts two different conformations for distinguishing host from viral RNA ligands.,Wang W, Pyle AM Mol Cell. 2022 Oct 13. pii: S1097-2765(22)00950-9. doi:, 10.1016/j.molcel.2022.09.029. PMID:36272408<ref>PMID:36272408</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>

OCA at 15:30, 7 September 2022

2022-09-07T15:30:45Z

← Older revision		Revision as of 15:30, 7 September 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 8dvs is ON HOLD		The entry 8dvs is ON HOLD until Paper Publication

	Authors:		Authors:

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

2022-08-10T04:03:46Z

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

← Older revision	Revision as of 04:03, 10 August 2022
(No difference)

OCA: New page: '''Unreleased structure''' The entry 8dvs is ON HOLD Authors: Description: Category: Unreleased Structures

2022-08-10T04:03:45Z

New page: '''Unreleased structure''' The entry 8dvs is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8dvs is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]