Department of Chemistry and Pharmacy, Institute of Physical and Theoretical Chemistry, University of Regensburg, 93040 Regensburg, Germany.
J Mol Model. 2012 Apr;18(4):1375-88. doi: 10.1007/s00894-011-1165-6. Epub 2011 Jul 15.
Phototropins are photoreceptors regulating the blue-light response in plants and bacteria. They consist of two LOV (light oxygen voltage sensitive) domains each containing a non-covalently bound flavin-mononucleotide (FMN) chromophore, which are connected to a serine/threonine-kinase. Upon illumination, the LOV-domains undergo conformational changes, triggering a signal cascade in the organism through kinase activation. Here, we present results from molecular dynamics simulations in which we investigate the signal transduction pathway of the wildtype LOV1-domain of Chlamydomonas reinhardtii and a methyl-mercaptan (MM) adduct of its Cys57Gly-mutant at the molecular level. In particular, we analyzed the effect of covalent-bond formation between the reactive cysteine Cys57 and the FMN-reaction center, as well as the subsequent charge redistribution, on the spatio-dynamical behavior of the LOV1-domain. We compare the calculation results with experimental data and demonstrate that these adduct state characteristics have an important influence on the response of this photosensor. The light-induced changes implicate primarily an alteration of the surface charge distribution through rearrangement of the highly flexible Cα-, Dα- and Eα-helices including the Glu51-Lys91-salt bridge on the hydrophilic side of the protein domain and a β-sheet tightening process via coupling of the Aβ- and Bβ-strands. Our findings confirm the aptitude of the LOV1-domain to function as a dimerization partner, allowing the green alga to adapt its reproduction and growth speed to the environmental conditions.
光受体是调节植物和细菌中蓝光反应的光感受器。它们由两个 LOV(光氧电压敏感)结构域组成,每个结构域都包含一个非共价结合的黄素单核苷酸(FMN)发色团,它们与丝氨酸/苏氨酸激酶相连。在光照下, LOV 结构域发生构象变化,通过激酶激活在生物体中引发信号级联。在这里,我们展示了分子动力学模拟的结果,其中我们在分子水平上研究了莱茵衣藻野生型 LOV1 结构域和其 Cys57Gly 突变体的甲基巯基(MM)加合物的信号转导途径。特别是,我们分析了反应性半胱氨酸 Cys57 与 FMN 反应中心之间形成共价键以及随后的电荷重新分布对 LOV1 结构域的时空动力学行为的影响。我们将计算结果与实验数据进行比较,并证明这些加合物状态特征对该光传感器的响应有重要影响。光诱导的变化主要通过高度灵活的 Cα、Dα 和 Eα 螺旋的重排,包括蛋白质结构域亲水侧的 Glu51-Lys91 盐桥,以及 Aβ 和 Bβ 链的耦合来改变表面电荷分布,从而导致β-片层收紧过程。我们的发现证实了 LOV1 结构域作为二聚化伴侣的能力,使绿藻能够适应其繁殖和生长速度的环境条件。