Sarcolipin Promotes Uncoupling of the SERCA Ca2+ Pump by Inducing a Structural Rearrangement in the Energy-Transduction Domain.
Biochemistry
; 55(44): 6083-6086, 2016 Nov 08.
Article
en En
| MEDLINE
| ID: mdl-27731980
We have performed microsecond (µs) molecular dynamics simulation (MDS) to identify structural mechanisms for sarcolipin (SLN) uncoupling of Ca2+ transport from ATP hydrolysis for the sarcoplasmic reticulum Ca2+-ATPase (SERCA). SLN regulates muscle metabolism and energy expenditure to provide resistance against diet-induced obesity and extreme cold. MDS demonstrated that the cytosolic domain of SLN induces a salt bridge-mediated structural rearrangement in the energy-transduction domain of SERCA. We propose that this structural change uncouples SERCA by perturbing Ca2+ occlusion at residue E309 in transport site II, thus facilitating Ca2+ backflux to the cytosol. Our results have important implications for designing muscle-based therapies for human obesity.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteolípidos
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Transducción de Señal
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Metabolismo Energético
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ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico
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Proteínas Musculares
Idioma:
En
Revista:
Biochemistry
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos