Activation-Induced Reorganization of Energy Transport Networks in the β 2 Adrenergic Receptor
Activation-Induced Reorganization of Energy Transport Networks in the β 2 Adrenergic Receptor
复制标题
β 2 肾上腺素受体中能量传输网络的激活诱导重组
DOI：
10.1021/acs.jpcb.1c03412
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Leitner, David M.
中科院分区：
文献类型：
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作者：
Poudel, Humanath;Leitner, David M.
基于β 2肾上腺素能受体（β2AR）的分子动力学模拟结果，计算了β 2AR（一种G蛋白偶联受体，GPCR）在非活性和活性状态下的能量交换网络（EENs）.我们引入了一个新的定义EENs的重组激活后，依赖于整个蛋白质的非共价接触的能量转移率的相对变化。基于我们获得的β2AR激活后的重组网络，我们确定了激动剂结合位点和胞质区域之间的分支途径，G蛋白在激活时与受体结合。该途径包括所有含有分子开关的基序，这些分子开关先前被鉴定为在激动剂结合后促进β2AR的变构转变。将EEN及其激活后的重组与针对β 2 AR的非活性和活性状态计算的基于结构的接触网络进行比较。
We compute energy exchange networks (EENs) through the β2adrenergic receptor (β2AR), a G-protein coupled receptor (GPCR), in inactive and active states, based on the results of molecular dynamics simulations of this membrane bound protein. We introduce a new definition for the reorganization of EENs upon activation that depends on the relative change in rates of energy transfer across noncovalent contacts throughout the protein. On the basis of the reorganized network that we obtain for β2AR upon activation, we identify a branched pathway between the agonist binding site and the cytoplasmic region, where a G-protein binds to the receptor when activated. The pathway includes all of the motifs containing molecular switches previously identified as contributing to the allosteric transition of β2AR upon agonist binding. EENs and their reorganization upon activation are compared with structure-based contact networks computed for the inactive and active states of β2AR.