6o31 - Revision history

OCA at 07:03, 11 October 2023

2023-10-11T07:03:28Z

←Older revision		Revision as of 07:03, 11 October 2023
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	<StructureSection load='6o31' size='340' side='right'caption='[[6o31]], [[Resolution\|resolution]] 1.51Å' scene=''>		<StructureSection load='6o31' size='340' side='right'caption='[[6o31]], [[Resolution\|resolution]] 1.51Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6o31]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O31 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6O31 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6o31]] is a 1 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=6O31 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6O31 FirstGlance]. <br>
-	</td></tr><tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~ACTN4 (~~[~~http://www~~.~~ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info~~&~~srchmode=5&id=9606 HUMAN])~~</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]] 1.51Å</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6o31 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o31 OCA], [~~http~~://pdbe.org/6o31 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6o31 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6o31 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6o31 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=6o31 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o31 OCA], [https://pdbe.org/6o31 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6o31 RCSB], [https://www.ebi.ac.uk/pdbsum/6o31 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6o31 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/ACTN4_HUMAN ACTN4_HUMAN] Defects in ACTN4 are the cause of focal segmental glomerulosclerosis type 1 (FSGS1) [MIM:[https://omim.org/entry/603278 603278]. A renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and edema. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation.<ref>PMID:10700177</ref>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/ACTN4_HUMAN ACTN4_HUMAN] F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein. Probably involved in vesicular trafficking via its association with the CART complex. The CART complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 6o31" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6o31" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Actinin 3D structures\|Actinin 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Birrane, G]]	+	[[Category: Birrane G]]
-	[[Category: Feng, D]]	+	[[Category: Feng D]]
-	~~[[Category: Actin- binding protein]]~~	+
-	~~[[Category: Actin-crosslinking]]~~	+
-	~~[[Category: Calponin homology domain]]~~	+
-	~~[[Category: Ch domain]]~~	+
-	~~[[Category: Disease mutation]]~~	+
-	~~[[Category: Glomeruloscleros spectrin family]]~~	+
-	~~[[Category: Nucleus]]~~	+
-	~~[[Category: Phosphorylation]]~~	+
-	~~[[Category: Structural protein~~]]	+

OCA at 09:50, 9 September 2020

2020-09-09T09:50:53Z

←Older revision		Revision as of 09:50, 9 September 2020
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	<StructureSection load='6o31' size='340' side='right'caption='[[6o31]], [[Resolution\|resolution]] 1.51Å' scene=''>		<StructureSection load='6o31' size='340' side='right'caption='[[6o31]], [[Resolution\|resolution]] 1.51Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6o31]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O31 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6O31 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6o31]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O31 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6O31 FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6o31 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o31 OCA], [http://pdbe.org/6o31 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6o31 RCSB], [http://www.ebi.ac.uk/pdbsum/6o31 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6o31 ProSAT]</span></td></tr>	+	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ACTN4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6o31 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o31 OCA], [http://pdbe.org/6o31 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6o31 RCSB], [http://www.ebi.ac.uk/pdbsum/6o31 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6o31 ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	BACKGROUND: Genetic mutations in alpha-actinin-4 (ACTN4)-an important actin crosslinking cytoskeletal protein that provides structural support for kidney podocytes-have been linked to proteinuric glomerulosclerosis in humans. However, the effect of post-translational modifications of ACTN4 on podocyte integrity and kidney function is not known. METHODS: Using mass spectrometry, we found that ACTN4 is phosphorylated at serine (S) 159 in human podocytes. We used phosphomimetic and nonphosphorylatable ACTN4 to comprehensively study the effects of this phosphorylation in vitro and in vivo. We conducted x-ray crystallography, F-actin binding and bundling assays, and immunofluorescence staining to evaluate F-actin alignment. Microfluidic organ-on-a-chip technology was used to assess for detachment of podocytes simultaneously exposed to fluid flow and cyclic strain. We then used CRISPR/Cas9 to generate mouse models and assessed for renal injury by measuring albuminuria and examining kidney histology. We also performed targeted mass spectrometry to determine whether high extracellular glucose or TGF-beta levels increase phosphorylation of ACTN4. RESULTS: Compared with the wild type ACTN4, phosphomimetic ACTN4 demonstrated increased binding and bundling activity with F-actin in vitro. Phosphomimetic Actn4 mouse podocytes exhibited more spatially correlated F-actin alignment and a higher rate of detachment under mechanical stress. Phosphomimetic Actn4 mice developed proteinuria and glomerulosclerosis after subtotal nephrectomy. Moreover, we found that exposure to high extracellular glucose or TGF-beta stimulates phosphorylation of ACTN4 at S159 in podocytes. CONCLUSIONS: These findings suggest that increased phosphorylation of ACTN4 at S159 leads to biochemical, cellular, and renal pathology that is similar to pathology resulting from human disease-causing mutations in ACTN4. ACTN4 may mediate podocyte injury as a consequence of both genetic mutations and signaling events that modulate phosphorylation.
		+
		+	Phosphorylation of ACTN4 Leads to Podocyte Vulnerability and Proteinuric Glomerulosclerosis.,Feng D, Kumar M, Muntel J, Gurley SB, Birrane G, Stillman IE, Ding L, Wang M, Ahmed S, Schlondorff J, Alper SL, Ferrante T, Marquez SL, Ng CF, Novak R, Ingber DE, Steen H, Pollak MR J Am Soc Nephrol. 2020 Jul;31(7):1479-1495. doi: 10.1681/ASN.2019101032. Epub, 2020 Jun 15. PMID:32540856<ref>PMID:32540856</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6o31" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Birrane, G]]		[[Category: Birrane, G]]

OCA at 09:17, 26 February 2020

2020-02-26T09:17:38Z

←Older revision		Revision as of 09:17, 26 February 2020
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-	'''Unreleased structure'''

-	~~The entry 6o31 is ON HOLD until Paper Publication~~	+	==CRYSTAL STRUCTURE OF THE ACTIN-BINDING DOMAIN OF HUMAN ALPHA-ACTININ-4==
-		+	<StructureSection load='6o31' size='340' side='right'caption='[[6o31]], [[Resolution\|resolution]] 1.51Å' scene=''>
-	~~Authors: Birrane, G., Feng, D.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6o31]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O31 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6O31 FirstGlance]. <br>
-	~~Description:~~ CRYSTAL STRUCTURE OF THE ACTIN-BINDING DOMAIN OF HUMAN ALPHA-ACTININ-4	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6o31 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o31 OCA], [http://pdbe.org/6o31 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6o31 RCSB], [http://www.ebi.ac.uk/pdbsum/6o31 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6o31 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Birrane, G]]
	[[Category: Feng, D]]		[[Category: Feng, D]]
-	[[Category: ~~Birrane, G~~]]	+	[[Category: Actin- binding protein]]
		+	[[Category: Actin-crosslinking]]
		+	[[Category: Calponin homology domain]]
		+	[[Category: Ch domain]]
		+	[[Category: Disease mutation]]
		+	[[Category: Glomeruloscleros spectrin family]]
		+	[[Category: Nucleus]]
		+	[[Category: Phosphorylation]]
		+	[[Category: Structural protein]]

OCA: Protected "6o31" [edit=sysop:move=sysop]

2019-03-06T05:42:46Z

Protected "6o31" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:42, 6 March 2019

OCA: New page: '''Unreleased structure''' The entry 6o31 is ON HOLD until Paper Publication Authors: Birrane, G., Feng, D. Description: CRYSTAL STRUCTURE OF THE ACTIN-BINDING DOMAIN OF HUMAN ALPHA-AC...

2019-03-06T05:42:44Z

New page: '''Unreleased structure''' The entry 6o31 is ON HOLD until Paper Publication Authors: Birrane, G., Feng, D. Description: CRYSTAL STRUCTURE OF THE ACTIN-BINDING DOMAIN OF HUMAN ALPHA-AC...

New page

'''Unreleased structure'''

The entry 6o31 is ON HOLD until Paper Publication

Authors: Birrane, G., Feng, D.

Description: CRYSTAL STRUCTURE OF THE ACTIN-BINDING DOMAIN OF HUMAN ALPHA-ACTININ-4
[[Category: Unreleased Structures]]
[[Category: Feng, D]]
[[Category: Birrane, G]]