Lemmon M A, Flanagan J M, Treutlein H R, Zhang J, Engelman D M
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06511.
Biochemistry. 1992 Dec 29;31(51):12719-25. doi: 10.1021/bi00166a002.
While several reports have suggested a role for helix-helix interactions in membrane protein oligomerization, there are few direct biochemical data bearing on this subject. Here, using mutational analysis, we show that dimerization of the transmembrane alpha-helix of glycophorin A in a detergent environment is spontaneous and highly specific. Very subtle changes in the side-chain structure at certain sensitive positions disrupt the helix-helix association. These sensitive positions occur at approximately every 3.9 residues along the helix, consistent with their comprising the interface of a closely fit transmembranous supercoil of alpha-helices. By contrast with other reported cases of interactions between transmembrane helices, the set of interfacial residues in this case contains no highly polar groups. Amino acids with aliphatic side chains define much of the interface, indicating that precise packing interactions between the helices may provide much of the energy for association. These data highlight the potential general importance of specific interactions between the hydrophobic anchors of integral membrane proteins.
虽然有几份报告表明螺旋-螺旋相互作用在膜蛋白寡聚化过程中发挥作用，但关于这一主题的直接生化数据却很少。在此，我们通过突变分析表明，在去污剂环境中，血型糖蛋白A跨膜α-螺旋的二聚化是自发且高度特异性的。某些敏感位置侧链结构的非常细微变化会破坏螺旋-螺旋缔合。这些敏感位置沿螺旋大约每3.9个残基出现一次，这与它们构成紧密契合的α-螺旋跨膜超螺旋界面相符。与其他报道的跨膜螺旋之间相互作用的情况不同，这种情况下的界面残基组不含高极性基团。具有脂肪族侧链的氨基酸界定了大部分界面，表明螺旋之间精确的堆积相互作用可能为缔合提供了大部分能量。这些数据突出了整合膜蛋白疏水锚之间特异性相互作用潜在的普遍重要性。
