Conserved cysteine dioxidation enhances membrane interaction of human Cl(-)intracellular channel 5
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F20%3A00533907" target="_blank" >RIV/61388971:_____/20:00533907 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/00216208:11310/20:10413570
Výsledek na webu
<a href="https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fj.202000399R" target="_blank" >https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fj.202000399R</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1096/fj.202000399R" target="_blank" >10.1096/fj.202000399R</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Conserved cysteine dioxidation enhances membrane interaction of human Cl(-)intracellular channel 5
Popis výsledku v původním jazyce
The human chloride intracellular channel (hCLIC) family is thought to transition between globular and membrane-associated forms by exposure of a hydrophobic surface. However, the molecular identity of this surface, and the triggering events leading to its exposure, remain elusive. Here, by combining biochemical and structural approaches, together with mass spectrometry (MS) analyses, we show that hCLIC5 is inherently flexible. X-ray crystallography revealed the existence of a globular conformation, while small-angle X-ray scattering showed additional elongated forms consisting of exposure of the conserved hydrophobic inter-domain interface to the bulk phase. Tryptophan fluorescence measurements demonstrated that the transition to the membrane-associated form is enhanced by the presence of oxidative environment and lipids. Using MS, we identified a dose-dependent oxidation of a highly conserved cysteine residue, known to play a key role in the structurally related omega-class of glutathione-S-transferases. Hydrogen/deuterium exchange MS analysis revealed that oxidation of this cysteine facilitates the exposure of the conserved hydrophobic inter-domain interface. Together, our results pinpoint an oxidation of a specific cysteine residue as a triggering mechanism initializing the molecular commitment for membrane interaction in the CLIC family.
Název v anglickém jazyce
Conserved cysteine dioxidation enhances membrane interaction of human Cl(-)intracellular channel 5
Popis výsledku anglicky
The human chloride intracellular channel (hCLIC) family is thought to transition between globular and membrane-associated forms by exposure of a hydrophobic surface. However, the molecular identity of this surface, and the triggering events leading to its exposure, remain elusive. Here, by combining biochemical and structural approaches, together with mass spectrometry (MS) analyses, we show that hCLIC5 is inherently flexible. X-ray crystallography revealed the existence of a globular conformation, while small-angle X-ray scattering showed additional elongated forms consisting of exposure of the conserved hydrophobic inter-domain interface to the bulk phase. Tryptophan fluorescence measurements demonstrated that the transition to the membrane-associated form is enhanced by the presence of oxidative environment and lipids. Using MS, we identified a dose-dependent oxidation of a highly conserved cysteine residue, known to play a key role in the structurally related omega-class of glutathione-S-transferases. Hydrogen/deuterium exchange MS analysis revealed that oxidation of this cysteine facilitates the exposure of the conserved hydrophobic inter-domain interface. Together, our results pinpoint an oxidation of a specific cysteine residue as a triggering mechanism initializing the molecular commitment for membrane interaction in the CLIC family.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10602 - Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology
Návaznosti výsledku
Projekt
Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.
Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2020
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
FASEB Journal
ISSN
0892-6638
e-ISSN
—
Svazek periodika
34
Číslo periodika v rámci svazku
8
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
16
Strana od-do
9925-9940
Kód UT WoS článku
000541773000001
EID výsledku v databázi Scopus
2-s2.0-85089440364