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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Buried lysine, but not arginine, titrates and alters transmembrane helix tilt
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Buried lysine, but not arginine, titrates and alters transmembrane helix tilt

机译:埋藏的赖氨酸而非精氨酸会滴定并改变跨膜螺旋倾斜

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摘要

The ionization states of individual amino acid residues of membrane proteins are difficult to decipher or assign directly in the lipid-bi-layer membrane environment. We address this issue for lysines and arginines in designed transmembrane helices. For lysines (but not arginines) at two locations within dioleoyl-phosphatidylcholine bi-layer membranes, we measure pK_a values below 7.0. We find that buried charged lysine, in fashion similar to arginine, will modulate helix orientation to maximize its own access to the aqueous interface or, if occluded by aromatic rings, may cause a transmembrane helix to exit the lipid bilayer. Interestingly, the influence of neutral lysine (vis-a-vis leucine) upon helix orientation also depends upon its aqueous access. Our results suggest that changes in the ionization states of particular residues will regulate membrane protein function and furthermore illustrate the subtle complexity of ionization behavior with respect to the detailed lipid and protein environment.
机译:膜蛋白的各个氨基酸残基的电离状态很难在脂双层膜环境中破译或直接分配。我们针对设计的跨膜螺旋中的赖氨酸和精氨酸解决此问题。对于二油酰基磷脂酰胆碱双层膜中两个位置的赖氨酸(而非精氨酸),我们测量的pK_a值低于7.0。我们发现,与精氨酸类似的方式,掩埋的带电荷的赖氨酸会调节螺旋的方向,以最大化其自身与水界面的接触,或者,如果被芳香环所阻塞,则可能导致跨膜螺旋离开脂质双层。有趣的是,中性赖氨酸(相对于亮氨酸)对螺旋取向的影响还取决于其水性。我们的结果表明特定残基电离状态的变化将调节膜蛋白的功能,并且进一步说明了相对于详细的脂质和蛋白质环境而言,电离行为的细微复杂性。

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