8g7n: Difference between revisions
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The entry | ==ATP- and mtHsp10-bound mtHsp60 V72I== | ||
<StructureSection load='8g7n' size='340' side='right'caption='[[8g7n]], [[Resolution|resolution]] 2.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8g7n]] is a 28 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=8G7N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8G7N 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]] 2.7Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=8g7n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8g7n OCA], [https://pdbe.org/8g7n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8g7n RCSB], [https://www.ebi.ac.uk/pdbsum/8g7n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8g7n ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/CH60_HUMAN CH60_HUMAN] Autosomal dominant spastic paraplegia type 13;Pelizaeus-Merzbacher-like disease due to HSPD1 mutation. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CH60_HUMAN CH60_HUMAN] Implicated in mitochondrial protein import and macromolecular assembly. May facilitate the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The mitochondrial chaperonin, mtHsp60, promotes the folding of newly imported and transiently misfolded proteins in the mitochondrial matrix, assisted by its co-chaperone mtHsp10. Despite its essential role in mitochondrial proteostasis, structural insights into how this chaperonin binds to clients and progresses through its ATP-dependent reaction cycle are not clear. Here, we determined cryo-electron microscopy (cryo-EM) structures of a hyperstable disease-associated mtHsp60 mutant, V72I, at three stages in this cycle. Unexpectedly, client density is identified in all states, revealing interactions with mtHsp60's apical domains and C-termini that coordinate client positioning in the folding chamber. We further identify a striking asymmetric arrangement of the apical domains in the ATP state, in which an alternating up/down configuration positions interaction surfaces for simultaneous recruitment of mtHsp10 and client retention. Client is then fully encapsulated in mtHsp60/mtHsp10, revealing prominent contacts at two discrete sites that potentially support maturation. These results identify a new role for the apical domains in coordinating client capture and progression through the cycle, and suggest a conserved mechanism of group I chaperonin function. | |||
Asymmetric apical domain states of mitochondrial Hsp60 coordinate substrate engagement and chaperonin assembly.,Braxton JR, Shao H, Tse E, Gestwicki JE, Southworth DR bioRxiv. 2023 May 15:2023.05.15.540872. doi: 10.1101/2023.05.15.540872. Preprint. PMID:37293102<ref>PMID:37293102</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8g7n" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Braxton JR]] | |||
[[Category: Gestwicki JE]] | |||
[[Category: Shao H]] | |||
[[Category: Southworth DR]] | |||
[[Category: Tse E]] | |||
Revision as of 10:23, 12 July 2023
ATP- and mtHsp10-bound mtHsp60 V72IATP- and mtHsp10-bound mtHsp60 V72I
Structural highlights
DiseaseCH60_HUMAN Autosomal dominant spastic paraplegia type 13;Pelizaeus-Merzbacher-like disease due to HSPD1 mutation. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. FunctionCH60_HUMAN Implicated in mitochondrial protein import and macromolecular assembly. May facilitate the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix. Publication Abstract from PubMedThe mitochondrial chaperonin, mtHsp60, promotes the folding of newly imported and transiently misfolded proteins in the mitochondrial matrix, assisted by its co-chaperone mtHsp10. Despite its essential role in mitochondrial proteostasis, structural insights into how this chaperonin binds to clients and progresses through its ATP-dependent reaction cycle are not clear. Here, we determined cryo-electron microscopy (cryo-EM) structures of a hyperstable disease-associated mtHsp60 mutant, V72I, at three stages in this cycle. Unexpectedly, client density is identified in all states, revealing interactions with mtHsp60's apical domains and C-termini that coordinate client positioning in the folding chamber. We further identify a striking asymmetric arrangement of the apical domains in the ATP state, in which an alternating up/down configuration positions interaction surfaces for simultaneous recruitment of mtHsp10 and client retention. Client is then fully encapsulated in mtHsp60/mtHsp10, revealing prominent contacts at two discrete sites that potentially support maturation. These results identify a new role for the apical domains in coordinating client capture and progression through the cycle, and suggest a conserved mechanism of group I chaperonin function. Asymmetric apical domain states of mitochondrial Hsp60 coordinate substrate engagement and chaperonin assembly.,Braxton JR, Shao H, Tse E, Gestwicki JE, Southworth DR bioRxiv. 2023 May 15:2023.05.15.540872. doi: 10.1101/2023.05.15.540872. Preprint. PMID:37293102[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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