8aiw - Revision history

OCA at 08:12, 7 February 2024

OCA — Wed, 07 Feb 2024 08:12:15 GMT

←Older revision		Revision as of 08:12, 7 February 2024
Line 9:		Line 9:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/O25273_HELPY O25273_HELPY]		[https://www.uniprot.org/uniprot/O25273_HELPY O25273_HELPY]
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	The bacterial human pathogen Helicobacter pylori produces a type IV secretion system (cagT4SS) to inject the oncoprotein CagA into gastric cells. The cagT4SS external pilus mediates attachment of the apparatus to the target cell and the delivery of CagA. While the composition of the pilus is unclear, CagI is present at the surface of the bacterium and required for pilus formation. Here, we have investigated the properties of CagI by an integrative structural biology approach. Using Alpha Fold 2 and Small Angle X-ray scattering, it was found that CagI forms elongated dimers mediated by rod-shape N-terminal domains (CagIN) prolonged by globular C-terminal domains (CagIC). Three Designed Ankyrin Repeat Proteins (DARPins) K2, K5 and K8 selected against CagI interacted with CagIC with subnanomolar affinities. The crystal structures of the CagI:K2 and CagI:K5 complexes were solved and identified the interfaces between the molecules, thereby providing a structural explanation for the difference in affinity between the two binders. Purified CagI and CagIC were found to interact with adenocarcinoma gastric (AGS) cells, induced cell spreading and the interaction was inhibited by K2. The same DARPin inhibited CagA translocation by up to 65% in AGS cells while inhibition levels were 40% and 30% with K8 and K5, respectively. Our study suggests that CagIC plays a key role in cagT4SS-mediated CagA translocation and that DARPins targeting CagI represent potent inhibitors of the cagT4SS, a crucial risk factor for gastric cancer development.
-
-	Designed Ankyrin Repeat Proteins provide insights into the structure and function of CagI and are potent inhibitors of CagA translocation by the Helicobacter pylori type IV secretion system.,Blanc M, Lettl C, Guerin J, Vieille A, Furler S, Briand-Schumacher S, Dreier B, Berge C, Pluckthun A, Vadon-Le Goff S, Fronzes R, Rousselle P, Fischer W, Terradot L PLoS Pathog. 2023 May 8;19(5):e1011368. doi: 10.1371/journal.ppat.1011368. PMID:37155700<ref>PMID:37155700</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 8aiw" style="background-color:#fffaf0;"></div>
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 10:14, 16 August 2023

OCA — Wed, 16 Aug 2023 10:14:27 GMT

←Older revision		Revision as of 10:14, 16 August 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[8aiw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Helicobacter_pylori_26695 Helicobacter pylori 26695] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8AIW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8AIW FirstGlance]. <br>		<table><tr><td colspan='2'>[[8aiw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Helicobacter_pylori_26695 Helicobacter pylori 26695] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8AIW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8AIW FirstGlance]. <br>
-	</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=8aiw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8aiw OCA], [https://pdbe.org/8aiw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8aiw RCSB], [https://www.ebi.ac.uk/pdbsum/8aiw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8aiw ProSAT]</span></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2Å</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=8aiw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8aiw OCA], [https://pdbe.org/8aiw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8aiw RCSB], [https://www.ebi.ac.uk/pdbsum/8aiw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8aiw ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==

OCA at 06:58, 18 May 2023

OCA — Thu, 18 May 2023 06:58:13 GMT

←Older revision		Revision as of 06:58, 18 May 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 8aiw is ~~ON HOLD until Paper~~ Publication	+	==Structure of the K5/CagI complex==
		+	<StructureSection load='8aiw' size='340' side='right'caption='[[8aiw]], [[Resolution\|resolution]] 2.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8aiw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Helicobacter_pylori_26695 Helicobacter pylori 26695] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8AIW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8AIW FirstGlance]. <br>
		+	</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=8aiw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8aiw OCA], [https://pdbe.org/8aiw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8aiw RCSB], [https://www.ebi.ac.uk/pdbsum/8aiw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8aiw ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/O25273_HELPY O25273_HELPY]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The bacterial human pathogen Helicobacter pylori produces a type IV secretion system (cagT4SS) to inject the oncoprotein CagA into gastric cells. The cagT4SS external pilus mediates attachment of the apparatus to the target cell and the delivery of CagA. While the composition of the pilus is unclear, CagI is present at the surface of the bacterium and required for pilus formation. Here, we have investigated the properties of CagI by an integrative structural biology approach. Using Alpha Fold 2 and Small Angle X-ray scattering, it was found that CagI forms elongated dimers mediated by rod-shape N-terminal domains (CagIN) prolonged by globular C-terminal domains (CagIC). Three Designed Ankyrin Repeat Proteins (DARPins) K2, K5 and K8 selected against CagI interacted with CagIC with subnanomolar affinities. The crystal structures of the CagI:K2 and CagI:K5 complexes were solved and identified the interfaces between the molecules, thereby providing a structural explanation for the difference in affinity between the two binders. Purified CagI and CagIC were found to interact with adenocarcinoma gastric (AGS) cells, induced cell spreading and the interaction was inhibited by K2. The same DARPin inhibited CagA translocation by up to 65% in AGS cells while inhibition levels were 40% and 30% with K8 and K5, respectively. Our study suggests that CagIC plays a key role in cagT4SS-mediated CagA translocation and that DARPins targeting CagI represent potent inhibitors of the cagT4SS, a crucial risk factor for gastric cancer development.

-	~~Authors: Blanc~~, M., ~~Guerin~~, J.	+	Designed Ankyrin Repeat Proteins provide insights into the structure and function of CagI and are potent inhibitors of CagA translocation by the Helicobacter pylori type IV secretion system.,Blanc M, Lettl C, Guerin J, Vieille A, Furler S, Briand-Schumacher S, Dreier B, Berge C, Pluckthun A, Vadon-Le Goff S, Fronzes R, Rousselle P, Fischer W, Terradot L PLoS Pathog. 2023 May 8;19(5):e1011368. doi: 10.1371/journal.ppat.1011368. PMID:37155700<ref>PMID:37155700</ref>

-	~~Description: Structure~~ of the K5/~~CagI complex~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Guerin, J~~]]	+	<div class="pdbe-citations 8aiw" style="background-color:#fffaf0;"></div>
-	[[Category: Blanc, M]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Helicobacter pylori 26695]]
		+	[[Category: Large Structures]]
		+	[[Category: Synthetic construct]]
		+	[[Category: Blanc M]]
		+	[[Category: Guerin J]]

OCA at 03:53, 10 August 2022

OCA — Wed, 10 Aug 2022 03:53:47 GMT

←Older revision		Revision as of 03:53, 10 August 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8aiw is ON HOLD	+	The entry 8aiw is ON HOLD until Paper Publication

	Authors: Blanc, M., Guerin, J.		Authors: Blanc, M., Guerin, J.

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

OCA — Wed, 03 Aug 2022 03:49:34 GMT

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

←Older revision

Revision as of 03:49, 3 August 2022

OCA: New page: '''Unreleased structure''' The entry 8aiw is ON HOLD Authors: Blanc, M., Guerin, J. Description: Structure of the K5/CagI complex Category: Unreleased Structures [[Category: Guerin...

OCA — Wed, 03 Aug 2022 03:49:33 GMT

New page: '''Unreleased structure''' The entry 8aiw is ON HOLD Authors: Blanc, M., Guerin, J. Description: Structure of the K5/CagI complex Category: Unreleased Structures [[Category: Guerin...

New page

'''Unreleased structure'''

The entry 8aiw is ON HOLD

Authors: Blanc, M., Guerin, J.

Description: Structure of the K5/CagI complex
[[Category: Unreleased Structures]]
[[Category: Guerin, J]]
[[Category: Blanc, M]]