Liu L P, Deber C M
Structural Biology and Biochemistry, Research Institute, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
J Biol Chem. 1998 Sep 11;273(37):23645-8. doi: 10.1074/jbc.273.37.23645.
Although the chains of amino acids in proteins that span the membrane are demonstrably helical and hydrophobic, little attention has been paid toward addressing the range of helical propensities of individual amino acids in the non-polar environment of membranes. Because it is inappropriate to apply soluble protein-based structure prediction algorithms to membrane proteins, we have used de novo designed peptides (KKAAAXAAAAAXAAWAAXAAAKKKK-amide, where X indicates one of the 20 commonly occurring amino acids) that mimic a protein membrane-spanning domain to determine the alpha-helical proclivity of each residue in the isotropic non-polar environment of n-butanol. Peptide helicities measured by circular dichroism spectroscopy were found to range from theta222 = -17,000 degrees (Pro) to -38,800 degrees (Ile) in n-butanol. The relative helicity of each amino acid is shown to be well correlated with its occurrence frequency in natural transmembrane segments, indicating that the helical propensity of individual residues in concert with their hydrophobicity may be a key determinant of the conformations of protein segments in membranes.
尽管跨膜蛋白质中的氨基酸链明显呈螺旋状且具有疏水性，但在膜的非极性环境中，对于单个氨基酸螺旋倾向范围的研究却很少受到关注。由于将基于可溶性蛋白质的结构预测算法应用于膜蛋白并不合适，我们使用了从头设计的肽（KKAAAXAAAAAXAAWAAXAAAKKKK-酰胺，其中X表示20种常见氨基酸之一）来模拟蛋白质跨膜结构域，以确定在正丁醇的各向同性非极性环境中每个残基的α-螺旋倾向。通过圆二色光谱法测得的肽螺旋度在正丁醇中范围为θ222 = -17,000度（脯氨酸）至-38,800度（异亮氨酸）。结果表明，每个氨基酸的相对螺旋度与其在天然跨膜片段中的出现频率密切相关，这表明单个残基的螺旋倾向与其疏水性共同作用可能是膜中蛋白质片段构象的关键决定因素。
