Mechanism of conformational coupling in SecA: Key role of hydrogen-bonding networks and water interactions.
Biochim Biophys Acta
; 1858(2): 374-85, 2016 Feb.
Article
em En
| MEDLINE
| ID: mdl-26607006
ABSTRACT
SecA uses the energy yielded by the binding and hydrolysis of adenosine triphosphate (ATP) to push secretory pre-proteins across the plasma membrane in bacteria. Hydrolysis of ATP occurs at the nucleotide-binding site, which contains the conserved carboxylate groups of the DEAD-box helicases. Although crystal structures provide valuable snapshots of SecA along its reaction cycle, the mechanism that ensures conformational coupling between the nucleotide-binding site and the other domains of SecA remains unclear. The observation that SecA contains numerous hydrogen-bonding groups raises important questions about the role of hydrogen-bonding networks and hydrogen-bond dynamics in long-distance conformational couplings. To address these questions, we explored the molecular dynamics of SecA from three different organisms, with and without bound nucleotide, in water. By computing two-dimensional hydrogen-bonding maps we identify networks of hydrogen bonds that connect the nucleotide-binding site to remote regions of the protein, and sites in the protein that respond to specific perturbations. We find that the nucleotide-binding site of ADP-bound SecA has a preferred geometry whereby the first two carboxylates of the DEAD motif bridge via hydrogen-bonding water. Simulations of a mutant with perturbed ATP hydrolysis highlight the water-bridged geometry as a key structural element of the reaction path.
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MEDLINE
Assunto principal:
Proteínas de Membrana Transportadoras
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Bacillus subtilis
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Proteínas de Bactérias
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Água
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Trifosfato de Adenosina
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Adenosina Trifosfatases
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Simulação de Dinâmica Molecular
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article