7b2g - Revision history

OCA at 07:51, 7 February 2024

2024-02-07T07:51:51Z

←Older revision		Revision as of 07:51, 7 February 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7b2g]] 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=7B2G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B2G FirstGlance]. <br>		<table><tr><td colspan='2'>[[7b2g]] 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=7B2G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B2G FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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]] 3Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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=7b2g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b2g OCA], [https://pdbe.org/7b2g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b2g RCSB], [https://www.ebi.ac.uk/pdbsum/7b2g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b2g 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=7b2g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b2g OCA], [https://pdbe.org/7b2g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b2g RCSB], [https://www.ebi.ac.uk/pdbsum/7b2g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b2g ProSAT]</span></td></tr>
	</table>		</table>
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	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/GDAP1_HUMAN GDAP1_HUMAN] Regulates the mitochondrial network by promoting mitochondrial fission.<ref>PMID:16172208</ref>		[https://www.uniprot.org/uniprot/GDAP1_HUMAN GDAP1_HUMAN] Regulates the mitochondrial network by promoting mitochondrial fission.<ref>PMID:16172208</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral polyneuropathy in humans, and its subtypes are linked to mutations in dozens of different genes, including the gene coding for ganglioside-induced differentiation-associated protein 1 (GDAP1). The main GDAP1-linked CMT subtypes are the demyelinating CMT4A and the axonal CMT2K. Over a hundred different missense CMT mutations in the GDAP1 gene have been reported. However, despite implications for mitochondrial fission and fusion, cytoskeletal interactions, and response to reactive oxygen species, the etiology of GDAP1-linked CMT is poorly understood at the protein level. Based on earlier structural data, CMT-linked mutations could affect intramolecular interaction networks within the GDAP1 protein. We carried out structural and biophysical analyses on several CMT-linked GDAP1 protein variants and describe new crystal structures of the autosomal recessive R120Q and the autosomal dominant A247V and R282H GDAP1 variants. These mutations reside in the structurally central helices âº3, âº7, and âº8. In addition, solution properties of the CMT mutants R161H, H256R, R310Q, and R310W were analysed. All disease variant proteins retain close to normal structure and solution behaviour. All mutations, apart from those affecting Arg310 outside the folded GDAP1 core domain, decreased thermal stability. In addition, a bioinformatics analysis was carried out to shed light on the conservation and evolution of GDAP1, which is an outlier member of the GST superfamily. GDAP1-like proteins branched early from the larger group of GSTs. Phylogenetic calculations could not resolve the exact early chronology, but the evolution of GDAP1 is roughly as old as the splits of archaea from other kingdoms. Many known CMT mutation sites involve conserved residues or interact with them. A central role for the âº6-âº7 loop, within a conserved interaction network, is identified for GDAP1 protein stability. To conclude, we have expanded the structural analysis on GDAP1, strengthening the hypothesis that alterations in conserved intramolecular interactions may alter GDAP1 stability and function, eventually leading to mitochondrial dysfunction, impaired protein-protein interactions, and neuronal degeneration.
-
-	Conserved intramolecular networks in GDAP1 are closely connected to CMT-linked mutations and protein stability.,Sutinen A, Paffenholz D, Nguyen GTT, Ruskamo S, Torda AE, Kursula P PLoS One. 2023 Apr 14;18(4):e0284532. doi: 10.1371/journal.pone.0284532. , eCollection 2023. PMID:37058526<ref>PMID:37058526</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 7b2g" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 17:10, 26 April 2023

2023-04-26T17:10:41Z

←Older revision		Revision as of 17:10, 26 April 2023
Line 1:		Line 1:

	==Crystal structure of R120Q GDAP1 mutant==		==Crystal structure of R120Q GDAP1 mutant==
-	<StructureSection load='7b2g' size='340' side='right'caption='[[7b2g]]' scene=''>	+	<StructureSection load='7b2g' size='340' side='right'caption='[[7b2g]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7B2G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B2G FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7b2g]] 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=7B2G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B2G 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=7b2g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b2g OCA], [https://pdbe.org/7b2g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b2g RCSB], [https://www.ebi.ac.uk/pdbsum/7b2g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b2g ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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=7b2g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b2g OCA], [https://pdbe.org/7b2g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b2g RCSB], [https://www.ebi.ac.uk/pdbsum/7b2g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b2g ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/GDAP1_HUMAN GDAP1_HUMAN] Charcot-Marie-Tooth disease type 2H;Autosomal recessive intermediate Charcot-Marie-Tooth disease type A;Autosomal dominant Charcot-Marie-Tooth disease type 2K;Autosomal recessive Charcot-Marie-Tooth disease with hoarseness;Charcot-Marie-Tooth disease type 4A. 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. The disease is caused by variants affecting the gene represented in this entry.
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/GDAP1_HUMAN GDAP1_HUMAN] Regulates the mitochondrial network by promoting mitochondrial fission.<ref>PMID:16172208</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral polyneuropathy in humans, and its subtypes are linked to mutations in dozens of different genes, including the gene coding for ganglioside-induced differentiation-associated protein 1 (GDAP1). The main GDAP1-linked CMT subtypes are the demyelinating CMT4A and the axonal CMT2K. Over a hundred different missense CMT mutations in the GDAP1 gene have been reported. However, despite implications for mitochondrial fission and fusion, cytoskeletal interactions, and response to reactive oxygen species, the etiology of GDAP1-linked CMT is poorly understood at the protein level. Based on earlier structural data, CMT-linked mutations could affect intramolecular interaction networks within the GDAP1 protein. We carried out structural and biophysical analyses on several CMT-linked GDAP1 protein variants and describe new crystal structures of the autosomal recessive R120Q and the autosomal dominant A247V and R282H GDAP1 variants. These mutations reside in the structurally central helices âº3, âº7, and âº8. In addition, solution properties of the CMT mutants R161H, H256R, R310Q, and R310W were analysed. All disease variant proteins retain close to normal structure and solution behaviour. All mutations, apart from those affecting Arg310 outside the folded GDAP1 core domain, decreased thermal stability. In addition, a bioinformatics analysis was carried out to shed light on the conservation and evolution of GDAP1, which is an outlier member of the GST superfamily. GDAP1-like proteins branched early from the larger group of GSTs. Phylogenetic calculations could not resolve the exact early chronology, but the evolution of GDAP1 is roughly as old as the splits of archaea from other kingdoms. Many known CMT mutation sites involve conserved residues or interact with them. A central role for the âº6-âº7 loop, within a conserved interaction network, is identified for GDAP1 protein stability. To conclude, we have expanded the structural analysis on GDAP1, strengthening the hypothesis that alterations in conserved intramolecular interactions may alter GDAP1 stability and function, eventually leading to mitochondrial dysfunction, impaired protein-protein interactions, and neuronal degeneration.
		+
		+	Conserved intramolecular networks in GDAP1 are closely connected to CMT-linked mutations and protein stability.,Sutinen A, Paffenholz D, Nguyen GTT, Ruskamo S, Torda AE, Kursula P PLoS One. 2023 Apr 14;18(4):e0284532. doi: 10.1371/journal.pone.0284532. , eCollection 2023. PMID:37058526<ref>PMID:37058526</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7b2g" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Kursula P]]		[[Category: Kursula P]]
	[[Category: Nguyen GTT]]		[[Category: Nguyen GTT]]
	[[Category: Sutinen A]]		[[Category: Sutinen A]]

OCA at 09:53, 8 December 2021

2021-12-08T09:53:24Z

←Older revision		Revision as of 09:53, 8 December 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7b2g ~~is ON HOLD until Paper Publication~~	+	==Crystal structure of R120Q GDAP1 mutant==
-		+	<StructureSection load='7b2g' size='340' side='right'caption='[[7b2g]]' scene=''>
-	~~Authors~~: ~~Nguyen~~, G.T.T., ~~Sutinen~~, A., ~~Kursula~~, P.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7B2G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B2G FirstGlance]. <br>
-	~~Description: Crystal structure of R120Q GDAP1 mutant~~	+	</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=7b2g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b2g OCA], [https://pdbe.org/7b2g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b2g RCSB], [https://www.ebi.ac.uk/pdbsum/7b2g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b2g ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Kursula, P]]	+	__TOC__
-	[[Category: ~~Sutinen, A~~]]	+	</StructureSection>
-	[[Category: ~~Nguyen, G.T.T~~]]	+	[[Category: Large Structures]]
		+	[[Category: Kursula P]]
		+	[[Category: Nguyen GTT]]
		+	[[Category: Sutinen A]]

OCA at 05:26, 6 January 2021

2021-01-06T05:26:20Z

←Older revision		Revision as of 05:26, 6 January 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7b2g is ON HOLD	+	The entry 7b2g is ON HOLD until Paper Publication

	Authors: Nguyen, G.T.T., Sutinen, A., Kursula, P.		Authors: Nguyen, G.T.T., Sutinen, A., Kursula, P.
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	Description: Crystal structure of R120Q GDAP1 mutant		Description: Crystal structure of R120Q GDAP1 mutant
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Sutinen, A]]
	[[Category: Kursula, P]]		[[Category: Kursula, P]]
		+	[[Category: Sutinen, A]]
	[[Category: Nguyen, G.T.T]]		[[Category: Nguyen, G.T.T]]

OCA: Protected "7b2g" [edit=sysop:move=sysop]

2020-12-02T05:37:15Z

Protected "7b2g" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:37, 2 December 2020

OCA: New page: '''Unreleased structure''' The entry 7b2g is ON HOLD Authors: Nguyen, G.T.T., Sutinen, A., Kursula, P. Description: Crystal structure of R120Q GDAP1 mutant [[Category: Unreleased Struc...

2020-12-02T05:37:13Z

New page: '''Unreleased structure''' The entry 7b2g is ON HOLD Authors: Nguyen, G.T.T., Sutinen, A., Kursula, P. Description: Crystal structure of R120Q GDAP1 mutant [[Category: Unreleased Struc...

New page

'''Unreleased structure'''

The entry 7b2g is ON HOLD

Authors: Nguyen, G.T.T., Sutinen, A., Kursula, P.

Description: Crystal structure of R120Q GDAP1 mutant
[[Category: Unreleased Structures]]
[[Category: Sutinen, A]]
[[Category: Kursula, P]]
[[Category: Nguyen, G.T.T]]