Molecular dynamics simulations disclose early stages of the photo-activation of cryptochrome 4
Molecular dynamics simulations disclose early stages of the photo-activation of cryptochrome 4
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DOI：
10.1088/1367-2630/aad70f
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发表时间：
2018-08-10
影响因子：
3.3
通讯作者：
Solov'yov, Ilia A.
中科院分区：
文献类型：
--
作者：
Kattnig, Daniel R.;Nielsen, Claus;Solov'yov, Ilia A.
鸟类似乎配备了一个依赖于光的、基于径向对的磁罗盘，它依赖于真正的量子过程。虽然感觉蛋白的身份仍然是推测性的，隐花色素4最近被确定为最吉祥的候选者。在这里，我们报告的全原子分子动力学（MD）模拟解决的结构重组，伴随着光还原的黄素辅因子在欧洲罗宾隐花色素4（ErCry 4）。广泛的MD模拟表明，ErCry 4的光活化诱导大规模的构象变化短（数百纳秒）的时间尺度。具体而言，光还原伴随着C-末端尾部的释放、FAD结合位点附近的结构重排以及N-末端部分的α-螺旋片段的显著形成。其中一些重排似乎暴露了潜在的磷酸化位点。我们描述的构象动力学的蛋白质使用基于图形的方法，是由残基的相邻性和它们的局部运动的相关性通知。这种方法揭示了密集耦合的重组实体，即图社区，这可能有助于有效的信号转导，由于高密度的枢纽。这些群落由少数高度重要的残基相互连接。网络方法清楚地识别了光活化后的重组位点，这些位点在重组网络中表现为突起或精致的桥梁。我们还发现，与D.在黑腹果蝇中，C-末端结构域的释放似乎与靠近FAD辅因子的组氨酸残基的转座无关。
Birds appear to be equipped with a light-dependent, radical-pair-based magnetic compass that relies on truly quantum processes. While the identity of the sensory protein has remained speculative, cryptochrome 4 has recently been identified as the most auspicious candidate. Here, we report on all-atom molecular dynamics (MD) simulations addressing the structural reorganisations that accompany the photoreduction of the flavin cofactor in the European robin cryptochrome 4 (ErCry4). Extensive MD simulations reveal that the photo-activation of ErCry4 induces large-scale conformational changes on short (hundreds of nanoseconds) timescales. Specifically, the photo-reduction is accompanied with the release of the C-terminal tail, structural rearrangements in the vicinity of the FAD-binding site, and the noteworthy formation of an alpha-helical segment at the N-terminal part. Some of these rearrangements appear to expose potential phosphorylation sites. We describe the conformational dynamics of the protein using a graph-based approach that is informed by the adjacency of residues and the correlation of their local motions. This approach reveals densely coupled reorganisation entities, i.e. graph communities, which could facilitate an efficient signal transduction due to a high density of hubs. These communities are interconnected by a small number of highly important residues. The network approach clearly identifies the sites restructuring upon photoactivation, which appear as protrusions or delicate bridges in the reorganisation network. We also find that, unlike in the homologous cryptochrome from D. melanogaster, the release of the C-terminal domain does not appear to be correlated with the transposition of a histidine residue close to the FAD cofactor.