Novel entropically driven conformation-specific interactions with Tomm34 modulate Hsp70 folding and ATPase activities

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F16%3AN0000021" target="_blank" >RIV/00209805:_____/16:N0000021 - isvavai.cz</a>

Výsledek na webu

<a href="http://www.mcponline.org/content/15/5/1710.long" target="_blank" >http://www.mcponline.org/content/15/5/1710.long</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1074/mcp.M116.058131" target="_blank" >10.1074/mcp.M116.058131</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Novel entropically driven conformation-specific interactions with Tomm34 modulate Hsp70 folding and ATPase activities

Popis výsledku v původním jazyce

Co-chaperones containing TPR domains enable cooperation between Hsp70 and Hsp90 to maintain cellular proteostasis. Whilst details of the molecular interactions between some TPR domains and Hsps are known, we describe a novel mechanism by which Tomm34 interacts with and coordinates Hsp70 activities. In contrast to previously defined Hop, Tomm34 interaction is dependent on the Hsp70 chaperone cycle. Tomm34 binds Hsp70 in a complex process: anchorage of the Hsp70 C-terminus by TPR1 domain is accompanied by additional contacts formed exclusively in ATP-bound state of Hsp70 resulting in a high-affinity entropically driven interaction. Tomm34 induces structural changes in determinants within the Hsp70-lid subdomain, modulates Hsp70/Hsp40-mediated refolding and Hsp40-stimulated Hsp70 ATPase activity. Since Tomm34 recruits Hsp90 through its TPR2 domain, we propose a model in which Tomm34 enables Hsp70/Hsp90 scaffolding and influences the Hsp70 chaperone cycle, providing an additional role for co-chaperones that contain multiple TPR domains in regulating protein homeostasis.

Název v anglickém jazyce

Novel entropically driven conformation-specific interactions with Tomm34 modulate Hsp70 folding and ATPase activities

Popis výsledku anglicky

Co-chaperones containing TPR domains enable cooperation between Hsp70 and Hsp90 to maintain cellular proteostasis. Whilst details of the molecular interactions between some TPR domains and Hsps are known, we describe a novel mechanism by which Tomm34 interacts with and coordinates Hsp70 activities. In contrast to previously defined Hop, Tomm34 interaction is dependent on the Hsp70 chaperone cycle. Tomm34 binds Hsp70 in a complex process: anchorage of the Hsp70 C-terminus by TPR1 domain is accompanied by additional contacts formed exclusively in ATP-bound state of Hsp70 resulting in a high-affinity entropically driven interaction. Tomm34 induces structural changes in determinants within the Hsp70-lid subdomain, modulates Hsp70/Hsp40-mediated refolding and Hsp40-stimulated Hsp70 ATPase activity. Since Tomm34 recruits Hsp90 through its TPR2 domain, we propose a model in which Tomm34 enables Hsp70/Hsp90 scaffolding and influences the Hsp70 chaperone cycle, providing an additional role for co-chaperones that contain multiple TPR domains in regulating protein homeostasis.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Molecular and cellular proteomics

ISSN

1535-9476

e-ISSN

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Svazek periodika

15

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

18

Strana od-do

1710-1727

Kód UT WoS článku

000375686100017

EID výsledku v databázi Scopus

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