Comparison of helix interactions in membrane and soluble α-bundle proteins
Comparison of helix interactions in membrane and soluble α-bundle proteins
复制标题
DOI：
10.1016/s0006-3495(02)75613-0
复制
发表时间：
2002-05-01
影响因子：
3.4
通讯作者：
Smith, SO
中科院分区：
文献类型：
--
作者：
Eilers, M;Patel, AB;Smith, SO
螺旋-螺旋相互作用对膜蛋白的折叠、稳定性和功能具有重要作用。在这里，两个独立和互补的方法被用来研究在膜和可溶性α-束蛋白中介导螺旋-螺旋相互作用的氨基酸的性质和分布。第一种方法基于被周围原子遮挡的范德华表面积来表征螺旋蛋白质中单个氨基酸的堆积密度。我们最近使用这种方法表明，平均而言，跨膜螺旋比可溶性蛋白质中的螺旋更紧密地堆积在一起。这些研究扩展到表征界面和非界面氨基酸的堆积，以及具有右手或左手交叉角、平行或反平行取向的螺旋的界面上的氨基酸堆积。我们发现膜蛋白中最丰富的紧密堆积的界面残基是Gly、Ala和Ser，并且平均而言，具有左旋交叉角的螺旋比具有右旋交叉角的螺旋更紧密地堆积。第二种用于表征螺旋-螺旋相互作用的方法涉及使用螺旋接触图。我们发现膜蛋白中的螺旋比可溶性蛋白质中的螺旋显示出更广泛的螺旋间接触分布。螺旋膜和可溶性蛋白质都利用一个主要依赖于四个残基(Leu、Ala、Ile、Val)的螺旋相互作用通用基序，以左旋螺旋螺旋的方式介导螺旋相互作用。然而，膜蛋白螺旋界面上小残基和极性残基(丙氨酸、甘氨酸、丝氨酸、苏氨酸)的高出现和高平均堆积值揭示了介导螺旋相互作用的第二个基序。最后，我们证明了螺旋-螺旋界面上残基的出现与它们的填充值之间存在很强的线性相关性，并从膜蛋白结构预测和膜蛋白稳定性方面对这些结果进行了讨论。
Helix-helix interactions are important for the folding, stability, and function of membrane proteins. Here, two independent and complementary methods are used to investigate the nature and distribution of amino acids that mediate helix-helix interactions in membrane and soluble alpha-bundle proteins. The first method characterizes the packing density of individual amino acids in helical proteins based on the van der Waals surface area occluded by surrounding atoms. We have recently used this method to show that transmembrane helices pack more tightly, on average, than helices in soluble proteins. These studies are extended here to characterize the packing of interfacial and noninterfacial amino acids and the packing of amino acids in the interfaces of helices that have either right- or left-handed crossing angles, and either parallel or antiparallel orientations. We show that the most abundant tightly packed interfacial residues in membrane proteins are Gly, Ala, and Ser, and that helices with left-handed crossing angles are more tightly packed on average than helices with right-handed crossing angles, The second method used to characterize helix-helix interactions involves the use of helix contact plots. We find that helices in membrane proteins exhibit a broader distribution of interhelical contacts than helices in soluble proteins. Both helical membrane and soluble proteins make use of a general motif for helix interactions that relies mainly on four residues (Leu, Ala, Ile, Val) to mediate helix interactions in a fashion characteristic of left-handed helical coiled coils. However, a second motif for mediating helix interactions is revealed by the high occurrence and high average packing values of small and polar residues (Ala, Gly, Ser, Thr) in the helix interfaces of membrane proteins. Finally, we show that there is a strong linear correlation between the occurrence of residues in helix-helix interfaces and their packing values, and discuss these results with respect to membrane protein structure prediction and membrane protein stability.