Eilers Markus, Patel Ashish B, Liu Wei, Smith Steven O
Department of Biochemistry and Cell Biology, Center for Structural Biology, SUNY Stony Brook, Stony Brook, New York 11794-5115, USA.
Biophys J. 2002 May;82(5):2720-36. doi: 10.1016/S0006-3495(02)75613-0.
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.
螺旋-螺旋相互作用对于膜蛋白的折叠、稳定性和功能至关重要。在此，我们使用了两种独立且互补的方法来研究介导膜蛋白和可溶性α-束蛋白中螺旋-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中的螺旋堆积得更紧密。在此将这些研究扩展，以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界面中氨基酸的堆积。我们表明，膜蛋白中最丰富的紧密堆积的界面残基是甘氨酸、丙氨酸和丝氨酸，并且平均而言，具有左手交叉角的螺旋比具有右手交叉角的螺旋堆积得更紧密。用于表征螺旋-螺旋相互作用的第二种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中的螺旋表现出更广泛的螺旋间接触分布。螺旋膜蛋白和可溶性蛋白都利用一种通用的螺旋相互作用基序，该基序主要依赖四个残基（亮氨酸、丙氨酸、异亮氨酸、缬氨酸）以左手螺旋卷曲螺旋的特征方式介导螺旋相互作用。然而，膜蛋白螺旋界面中小的极性残基（丙氨酸、甘氨酸、丝氨酸、苏氨酸）的高出现频率和高平均堆积值揭示了第二种介导螺旋相互作用的基序。最后，我们表明螺旋-螺旋界面中残基的出现频率与其堆积值之间存在很强的线性相关性，并就膜蛋白结构预测和膜蛋白稳定性讨论了这些结果。
