利用結構堆疊度論穿膜蛋白質之演化

Abstract

穿膜蛋白質與酵素相比具有相當不同摺疊方法，根據這個原因使穿膜蛋白有別於酵素擁有截然不同的生物物理特性與演化關係。最近幾年我們實驗室的研究發現，在酵素中蛋白質結構堆疊的緊密程度可以指出胺基酸的序列保留程度。藉由這個假設，我們嘗試在穿膜蛋白中驗證蛋白質結構堆疊程度與序列保留程度的相關性。在本篇論文中，我們的結果顯示，在75個穿膜蛋白質的結構中，結構堆疊程度與序列保留程度有良好的正相關，另外，我們觀察到蛋白質結構堆疊度也能反映出類似酵素結構的演化耦合影響。除此之外，以前的文獻中指出蛋白質結構穿膜的區域與膜外區域相比的演化速度較慢，我們利用蛋白質結構堆疊度分析得到穿膜區域的結構比膜外的區域緊密，這顯示結構的緊密度可能與蛋白質穿膜區域演化速度相較緩慢有著相當程度的關連。本篇論文的結果指出，就算有截然不同的堆疊方法，根據蛋白質結構的堆疊程度仍然可以在穿膜蛋白結構中得到演化資訊，以及穿膜蛋白結構的緊密度可能是影響穿膜區域演化緩慢重要的因素。

Membrane proteins have the distinctly different structural folding ways from enzyme proteins, resulting in difference between evolutionary information and respective biophysical properties. Recently, Our lab has shown the structural packing profiles of enzymes are quantitatively linked with the sequence conservation profiles of them. In this study, we calculated the weighted contact numbers of membrane proteins as structural packing profiles. Here, we reported the highly average correlation coefficient between the weighted contact number profiles and the sequence conservation profiles in a membrane protein dataset containing 75 membrane proteins with beta-barrel proteins and alpha-helical proteins, and the results could be observed that the structural packing of membrane proteins shows evolution coupling with other subunits. Some previous studies indicated that the evolutionary rate in transmembrane regions is slower than that in extramembrane regions. Using the structural packing analysis, the packing degree in transmembrane regions is also higher than that in extramembrane regions. That implies the structural packing has relevance to evolutionary rate in transmembrane regions. These results showed that the structural packing of membrane proteins might contain evolutionary information even if the folding ways of membrane proteins is different from enzyme, and might indicate that the structural packing of structure could be responsible for the slow evolutionary rates in transmembrane regions.