Molecular mechanism of long-range synergetic color tuning between multiple amino acid residues in conger rhodopsin.
Molecular mechanism of long-range synergetic color tuning between multiple amino acid residues in conger rhodopsin.
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DOI：
10.2142/biophysics.6.67
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发表时间：
2010-01-01
期刊：
影响因子：
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通讯作者：
Yamato T
中科院分区：
文献类型：
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作者：
Watanabe HC;Mori Y;Tada T;Yokoyama S;Yamato T
多个视紫红质突变对颜色调节的协同作用需要完全阐明。系统的遗传学研究和光谱分析已经证明了Conger视紫红质祖先色素(P501)中两个氨基酸残基之间协同调色的有趣例子：-一个近距离和一个远距离残基的双突变导致显著的λ最大蓝移13 nm，而这两个位点的单一突变都没有导致有意义的变化。为了分析这种协同调色的分子机制，我们进行了同源建模、分子模拟和电子态计算。对双突变体N195A/A292S进行的电子突变分析显示，视网膜生色团结构发生了明显变化，而单突变体A292S的结构几乎没有变化。利用QM/MM优化结构的统计集成，对三种视觉色素的视网膜发色团的激发能进行了估算。结果表明，p501的双突变体(DM)的λ最大位移为−8 nm，而单突变体(SM)的DNA最大位移为+1 nm。DM的分子动力学模拟表明，6-S-顺式和6-S-反式异构体的异构化频繁。然而，出乎意料的是，两种构象的激发能几乎相同，而主成分分析(PCA)证实了视网膜-反离子的协同变化(BLA)和视网膜-反离子的相互作用导致了这种位移。
The synergetic effects of multiple rhodopsin mutations on color tuning need to be completely elucidated. Systematic genetic studies and spectroscopy have demonstrated an interesting example of synergetic color tuning between two amino acid residues in conger rhodopsin’s ancestral pigment (p501): — a double mutation at one nearby and one distant residue led to a significant λmax blue shift of 13 nm, whereas neither of the single mutations at these two sites led to meaningful shifts. To analyze the molecular mechanisms of this synergetic color tuning, we performed homology modeling, molecular simulations, and electronic state calculations. For the double mutant, N195A/A292S, in silico mutation analysis demonstrated conspicuous structural changes in the retinal chromophore, whereas that of the single mutant, A292S, was almost unchanged. Using statistical ensembles of QM/MM optimized structures, the excitation energy of retinal chromophore was evaluated for the three visual pigments. As a result, the λmax shift of double mutant (DM) from p501 was −8 nm, while that of single mutant (SM) from p501 was +1 nm. Molecular dynamics simulation for DM demonstrated frequent isomerization between 6-s-cis and 6-s-trans conformers. Unexpectedly, however, the two conformers exhibited almost identical excitation energy, whereas principal component analysis (PCA) identified the retinal-counterion cooperative change of BLA (bond length alternation) and retinal-counterion interaction lead to the shift.