School of Chemistry and Molecular Biosciences, Faculty of Science, The University of Queensland, Brisbane, QLD 4072, Australia.
Proteins. 2010 Apr;78(5):1163-74. doi: 10.1002/prot.22636.
Atomistic molecular dynamics simulations have been used to investigate the conformational changes associated with the binding of human growth hormone (hGH) to the extracellular domains (ECD) of the human growth hormone receptor (hGHR), thereby shedding light on the mechanism of activation. It is shown that the removal of hGH from the hormone-bound receptor complex results in a counter-clockwise rotation of the twosubunits relative to each other by 30 degrees -64 degrees (average 45 degrees +/- 14 degrees), in close agreement in terms of both the magnitude and direction of the rotation with that proposed based on mutagenesis experiments. In addition to providing evidence to support a rotational activation mechanism, the simulations have enabled the nature of the interaction interfaces in both the cytokine-bound and unliganded hGHR states to be analyzed in detail.
运用原子分子动力学模拟研究了人生长激素（hGH）与人生长激素受体（hGHR）胞外结构域（ECD）结合所引起的构象变化，从而揭示了其激活机制。研究表明，hGH 从激素结合受体复合物中释放出来，导致两个亚基相对于彼此逆时针旋转 30 度至 64 度（平均 45 度±14 度），在旋转幅度和方向上与基于诱变实验提出的旋转激活机制非常吻合。这些模拟不仅为旋转激活机制提供了证据，还能够详细分析细胞因子结合和非配体结合的 hGHR 状态下相互作用界面的性质。
