OCA at 13:01, 1 November 2023

2023-11-01T13:01:37Z

←Older revision		Revision as of 13:01, 1 November 2023
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-	'''Unreleased structure'''

-	The entry ~~7x1i~~ is ~~ON HOLD~~	+	==Cryo-EM structure of human BTR1 in the outward-facing state.==
		+	<StructureSection load='7x1i' size='340' side='right'caption='[[7x1i]], [[Resolution\|resolution]] 2.94Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7x1i]] 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=7X1I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7X1I 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]] 2.94Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PT5:(1S)-2-{[(R)-HYDROXY{[(1R,2R,3S,4R,5R,6S)-2,3,6-TRIHYDROXY-4,5-BIS(PHOSPHONOOXY)CYCLOHEXYL]OXY}PHOSPHORYL]OXY}-1-[(OCTADECANOYLOXY)METHYL]ETHYL+(8E,11E)-ICOSA-5,8,11,14-TETRAENOATE'>PT5</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=7x1i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7x1i OCA], [https://pdbe.org/7x1i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7x1i RCSB], [https://www.ebi.ac.uk/pdbsum/7x1i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7x1i ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/S4A11_HUMAN S4A11_HUMAN] Corneal dystrophy-perceptive deafness syndrome;Fuchs endothelial corneal dystrophy;Congenital hereditary endothelial dystrophy type II. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/S4A11_HUMAN S4A11_HUMAN] Multifunctional transporter with an impact in cell morphology and differentiation. In the presence of borate B(OH)4(-), acts as a voltage-dependent electrogenic Na(+)-coupled B(OH)4(-) cotransporter controlling boron homeostasis (PubMed:15525507). At early stages of stem cell differentiation, participates in synergy with ITGA5-ITGB1 and ITGAV-ITGB3 integrins and BMPR1A to promote cell adhesion and contractility that drives differentiation toward osteogenic commitment while inhibiting adipogenesis (By similarity). In the absence of B(OH)4(-), acts as a Na(+)-coupled OH(-) or H(+) permeable channel with implications in cellular redox balance (PubMed:15525507, PubMed:28642546). Regulates the oxidative stress response in corneal endothelium by enhancing antioxidant defenses and protecting cells from reactive oxygen species (PubMed:28642546). In response to hypo-osmotic challenge, also acts as water permeable channel at the basolateral cell membrane of corneal endothelial cells and facilitates transendothelial fluid reabsorption in the aqueous humor (PubMed:31273259, PubMed:25007886, PubMed:23813972). In the presence of ammonia, acts as an electrogenic NH3/H(+) cotransporter and may play a role in ammonia transport and reabsorption in renal Henle's loop epithelium (PubMed:27581649).[UniProtKB:A2AJN7]<ref>PMID:15525507</ref> <ref>PMID:23813972</ref> <ref>PMID:25007886</ref> <ref>PMID:27581649</ref> <ref>PMID:28642546</ref> <ref>PMID:31273259</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	BTR1 (SLC4A11) is a NH(3) stimulated H(+) (OH(-)) transporter belonging to the SLC4 family. Dysfunction of BTR1 leads to diseases such as congenital hereditary endothelial dystrophy (CHED) and Fuchs endothelial corneal dystrophy (FECD). However, the mechanistic basis of BTR1 activation by alkaline pH, transport activity regulation and pathogenic mutations remains elusive. Here, we present cryo-EM structures of human BTR1 in the outward-facing state in complex with its activating ligands PIP(2) and the inward-facing state with the pathogenic R125H mutation. We reveal that PIP(2) binds at the interface between the transmembrane domain and the N-terminal cytosolic domain of BTR1. Disruption of either the PIP(2) binding site or protonation of PIP(2) phosphate groups by acidic pH can transform BTR1 into an inward-facing conformation. Our results provide insights into the mechanisms of how the transport activity and conformation changes of BTR1 are regulated by PIP(2) binding and interaction of TMD and NTD.

-	~~Authors~~:	+	Structural insights into the conformational changes of BTR1/SLC4A11 in complex with PIP(2).,Lu Y, Zuo P, Chen H, Shan H, Wang W, Dai Z, Xu H, Chen Y, Liang L, Ding D, Jin Y, Yin Y Nat Commun. 2023 Oct 3;14(1):6157. doi: 10.1038/s41467-023-41924-0. PMID:37788993<ref>PMID:37788993</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 7x1i" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Lu Y]]
		+	[[Category: Yin Y]]
		+	[[Category: Zuo P]]

OCA at 10:40, 4 October 2023

2023-10-04T10:40:27Z

←Older revision		Revision as of 10:40, 4 October 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7x1i is ON HOLD ~~until 2024-08-24~~	+	The entry 7x1i is ON HOLD

	Authors:		Authors:

OCA at 05:31, 22 March 2023

2023-03-22T05:31:10Z

←Older revision		Revision as of 05:31, 22 March 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7x1i is ON HOLD	+	The entry 7x1i is ON HOLD until 2024-08-24

	Authors:		Authors:

OCA: Protected "7x1i" [edit=sysop:move=sysop]

2022-03-02T05:16:45Z

Protected "7x1i" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:16, 2 March 2022

OCA: New page: '''Unreleased structure''' The entry 7x1i is ON HOLD Authors: Description: Category: Unreleased Structures

2022-03-02T05:16:44Z

New page: '''Unreleased structure''' The entry 7x1i is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7x1i is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

7x1i - Revision history

OCA at 13:01, 1 November 2023

OCA at 10:40, 4 October 2023

OCA at 05:31, 22 March 2023

OCA: Protected "7x1i" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7x1i is ON HOLD Authors: Description: Category: Unreleased Structures