Computer modelling reveals new conformers of the ATP binding loop of Na+/K+-ATPase involved in the transphosphorylation process of the sodium pump

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F17%3A00477214" target="_blank" >RIV/68378041:_____/17:00477214 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/17:10373843 RIV/62157124:16170/17:43875785 RIV/68407700:21720/17:00327507

Výsledek na webu

<a href="http://dx.doi.org/10.7717/peerj.3087" target="_blank" >http://dx.doi.org/10.7717/peerj.3087</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.7717/peerj.3087" target="_blank" >10.7717/peerj.3087</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Computer modelling reveals new conformers of the ATP binding loop of Na+/K+-ATPase involved in the transphosphorylation process of the sodium pump

Popis výsledku v původním jazyce

Hydrolysis of ATP by Na+/K+-ATPase, a P-Type ATPase, catalyzing active Na+ and K+ transport through cellular membranes leads transiently to a phosphorylation of its catalytical alpha-subunit. Surprisingly, three-dimensional molecular structure analysis of P-type ATPases reveals that binding of ATP to the N-domain connected by a hinge to the P-domain is much too far away from the Asp(369) to allow the transfer of ATP's terminal phosphate to its aspartyl-phosphorylation site. In order to get information for how the transfer of the gamma-phosphate group of ATP to the Asp(369) is achieved, analogous molecular modeling of the M-4 M-5 loop of ATPase was performed using the crystal data of Na+/K+-ATPase of different species. Analogous molecular modeling of the cytoplasmic loop between Thr(338) and Ile(760) of the a alpha-subunit of Na+/K+-ATPase and the analysis of distances between the ATP binding site and phosphorylation site revealed the existence of two ATP binding sites in the open conformation, the first one close to Phe(475) in the N-domain, the other one close to Asp(369) in the 13-domain. However, binding of Mg2+circle ATP to any of these sites in the open conformation may not lead to phosphorylation of Asp(369). Additional conformations of the cytoplasmic loop were found wobbling between open conformation <==> semi-open conformation <==> closed conformation in the absence of 2Mg(2+)circle ATP. The cytoplasmic loop's conformational change to the semi-open conformatio characterized by a hydrogen bond between Arg(543) and Asp(611) triggers by binding of 2Mg(2+)circle ATP Ito a single ATP l site and conversion to the closed l conformation the phosphorylation of Asp(369) in the P-domain, and hence the start of Na+/K+-activated ATP hydrolysis.

Název v anglickém jazyce

Computer modelling reveals new conformers of the ATP binding loop of Na+/K+-ATPase involved in the transphosphorylation process of the sodium pump

Popis výsledku anglicky

Hydrolysis of ATP by Na+/K+-ATPase, a P-Type ATPase, catalyzing active Na+ and K+ transport through cellular membranes leads transiently to a phosphorylation of its catalytical alpha-subunit. Surprisingly, three-dimensional molecular structure analysis of P-type ATPases reveals that binding of ATP to the N-domain connected by a hinge to the P-domain is much too far away from the Asp(369) to allow the transfer of ATP's terminal phosphate to its aspartyl-phosphorylation site. In order to get information for how the transfer of the gamma-phosphate group of ATP to the Asp(369) is achieved, analogous molecular modeling of the M-4 M-5 loop of ATPase was performed using the crystal data of Na+/K+-ATPase of different species. Analogous molecular modeling of the cytoplasmic loop between Thr(338) and Ile(760) of the a alpha-subunit of Na+/K+-ATPase and the analysis of distances between the ATP binding site and phosphorylation site revealed the existence of two ATP binding sites in the open conformation, the first one close to Phe(475) in the N-domain, the other one close to Asp(369) in the 13-domain. However, binding of Mg2+circle ATP to any of these sites in the open conformation may not lead to phosphorylation of Asp(369). Additional conformations of the cytoplasmic loop were found wobbling between open conformation <==> semi-open conformation <==> closed conformation in the absence of 2Mg(2+)circle ATP. The cytoplasmic loop's conformational change to the semi-open conformatio characterized by a hydrogen bond between Arg(543) and Asp(611) triggers by binding of 2Mg(2+)circle ATP Ito a single ATP l site and conversion to the closed l conformation the phosphorylation of Asp(369) in the P-domain, and hence the start of Na+/K+-activated ATP hydrolysis.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10602 - Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology

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

2017

Kód důvěrnosti údajů

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

Název periodika

PeerJ

ISSN

2167-8359

e-ISSN

—

Svazek periodika

5

Číslo periodika v rámci svazku

mar

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

22

Strana od-do

—

Kód UT WoS článku

000396906100007

EID výsledku v databázi Scopus

2-s2.0-85015203992