Sarcolipin Promotes Uncoupling of the SERCA Ca2+ Pump by Inducing a Structural Rearrangement in the Energy-Transduction Domain

被引：35

作者：

Autry, Joseph M. ^{[1
,2
]}

Thomas, David D. ^{[1
]}

Espinoza-Fonseca, L. Michel ^{[1
]}

机构：

[1] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA

[2] Univ Minnesota, Biophys Technol Ctr, Minneapolis, MN 55455 USA

来源：

BIOCHEMISTRY | 2016年 / 55卷 / 44期

基金：

美国国家卫生研究院;

关键词：

SARCOPLASMIC-RETICULUM CA2+-ATPASE; MUSCLE-BASED THERMOGENESIS; CALCIUM-PUMP; SKELETAL-MUSCLE; CRYSTAL-STRUCTURES; ATPASE SERCA; PHOSPHOLAMBAN; TRANSPORT; INHIBITION; BINDING;

D O I：

10.1021/acs.biochem.6b00728

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have performed microsecond (its) 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.

引用

页码：6083 / +

页数：4

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