Membrane environment imposes unique selection pressures on transmembrane domains of G protein-coupled receptors.
Membrane environment imposes unique selection pressures on transmembrane domains of G protein-coupled receptors.
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DOI：
10.1007/s00239-012-9538-8
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发表时间：
2013-03
影响因子：
3.9
通讯作者：
Wilke, Claus O.
中科院分区：
文献类型：
--
作者：
Spielman, Stephanie J.;Wilke, Claus O.
我们研究了质膜环境对G蛋白偶联受体（GPCRs）分子进化的影响，GPCRs是后生动物中最大的受体家族。特别是，我们分析了这些膜蛋白的两个主要结构分区——跨膜（TM）区和膜外（EM）区的位点特异性速率变化。我们发现跨膜结构域的进化比膜外结构域慢，尽管TM结构域相对于其EM对应结构域显示出更高的速率异质性。尽管GPCRs中的大多数残基经历了从强到弱的纯化选择，但许多GPCRs在TM和EM残基上都经历了正选择，尽管略微偏向于EM。此外，一部分GPCRs，即化学感觉受体（包括嗅觉和味觉受体），相对于其他GPCRs表现出更高的进化速率，这种效应在其TM跨膜区更为明显。尽管先前有人认为TM的低进化速率是由于其埋藏残基的高比例所致，但我们表明其减缓的速率似乎源于膜本身的强烈生物物理限制，或者源于功能需求。尽管存在强烈的进化限制作用于GPCRs的跨膜跨区，但正选择和高水平的进化速率变异性是常见的。因此，不应假定生物物理限制会排除蛋白质的进化能力。
蛋白质进化 G蛋白偶联受体 膜蛋白 正选择
We have investigated the influence of the plasma membrane environment on the molecular evolution of G protein-coupled receptors (GPCRs), the largest receptor family in Metazoa. In particular, we have analyzed the site-specific rate variation across the two primary structural partitions, transmembrane (TM) and extramembrane (EM), of these membrane proteins. We find that transmembrane domains evolve more slowly than do extramembrane domains, though TM domains display increased rate heterogeneity relative to their EM counterparts. Although the majority of residues across GPCRs experience strong to weak purifying selection, many GPCRs experience positive selection at both TM and EM residues, albeit with a slight bias towards the EM. Further, a subset of GPCRs, chemosensory receptors (including olfactory and taste receptors), exhibit increased rates of evolution relative to other GPCRs, an effect which is more pronounced in their TM spans. Although it has been previously suggested that the TM’s low evolutionary rate is caused by their high percentage of buried residues, we show that their attenuated rate seems to stem from the strong biophysical constraints of the membrane itself, or by functional requirements. In spite of the strong evolutionary constraints acting on the transmembrane spans of GPCRs, positive selection and high levels of evolutionary rate variability are common. Thus, biophysical constraints should not be presumed to preclude a protein’s ability to evolve. Protein evolution G protein-coupled receptors Membrane proteins Positive selection
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影响因子：
7
作者：
Gilad, Y;Man, O;Glusman, G
通讯作者：
Glusman, G
影响因子：
3.6
作者：
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通讯作者：
Schiöth, HB
影响因子：
6.8
作者：
AKAIKE, H
通讯作者：
AKAIKE, H
影响因子：
4.8
作者：
Lu, ZL;Hulme, EC
通讯作者：
Hulme, EC
DOI：
10.1073/pnas.1635157100
发表时间：
2003-10-14
影响因子：
11.1
作者：
Niimura, Y;Nei, M
通讯作者：
Nei, M