Water-Gated Proton Transfer Dynamics in Respiratory Complex I.
J Am Chem Soc
; 142(32): 13718-13728, 2020 08 12.
Article
em En
| MEDLINE
| ID: mdl-32643371
ABSTRACT
The respiratory complex I transduces redox energy into an electrochemical proton gradient in aerobic respiratory chains, powering energy-requiring processes in the cell. However, despite recently resolved molecular structures, the mechanism of this gigantic enzyme remains poorly understood. By combining large-scale quantum and classical simulations with site-directed mutagenesis and biophysical experiments, we show here how the conformational state of buried ion-pairs and water molecules control the protonation dynamics in the membrane domain of complex I and establish evolutionary conserved long-range coupling elements. We suggest that an electrostatic wave propagates in forward and reverse directions across the 200 Å long membrane domain during enzyme turnover, without significant dissipation of energy. Our findings demonstrate molecular principles that enable efficient long-range proton-electron coupling (PCET) and how perturbation of this PCET machinery may lead to development of mitochondrial disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Prótons
/
Água
/
Complexo I de Transporte de Elétrons
/
Simulação de Dinâmica Molecular
Idioma:
En
Revista:
J Am Chem Soc
Ano de publicação:
2020
Tipo de documento:
Article