Stevens T J, Arkin I T
Cambridge Centre for Molecular Recognition, Department of Biochemistry, University of Cambridge, United Kingdom.
Proteins. 1999 Jul 1;36(1):135-43. doi: 10.1002/(sici)1097-0134(19990701)36:1<135::aid-prot11>3.0.co;2-i.
One of the central paradigms of structural biology is that membrane proteins are "inside-out" proteins, in that they have a core of polar residues surrounded by apolar residues. This is the reverse of the characteristics found in water-soluble proteins. We have decided to test this paradigm, now that sufficient numbers of transmembrane alpha-helical structures are accessible to statistical analysis. We have analyzed the correlation between accessibility and hydrophobicity of both individual residues and complete helices. Our analyses reveal that hydrophobicity of residues in a transmembrane helical bundle does not correlate with any preferred location and that the hydrophilic vector of a helix is a poor indicator of the solvent exposed face of a helix. Neither polar nor hydrophobic residues show any bias for the exterior or the interior of a transmembrane domain. As a control, analysis of water-soluble helical bundles performed in a similar manner has yielded clear correlations between hydrophobicity and accessibility. We therefore conclude that, based on the data set used, membrane proteins as "inside-out" proteins is an unfounded notion, suggesting that packing of alpha-helices in membranes is better understood by maximization of van der Waal's forces, rather than by a general segregation of hydrophobicities driven by lipid exclusion.
结构生物学的核心范式之一是膜蛋白是“由内而外”的蛋白质，即它们有一个由非极性残基包围的极性残基核心。这与水溶性蛋白质的特征相反。既然现在有足够数量的跨膜α螺旋结构可供统计分析，我们决定测试这一范式。我们分析了单个残基和完整螺旋的可及性与疏水性之间的相关性。我们的分析表明，跨膜螺旋束中残基的疏水性与任何偏好位置均无关联，并且螺旋的亲水性向量并不能很好地指示螺旋的溶剂暴露面。极性和非极性残基在跨膜结构域的外部或内部均无任何偏向性。作为对照，以类似方式对水溶性螺旋束进行的分析得出了疏水性与可及性之间的明确相关性。因此，我们得出结论，基于所使用的数据集，认为膜蛋白是“由内而外”的蛋白质这一观点是没有根据的，这表明通过最大化范德华力能更好地理解膜中α螺旋的堆积，而不是由脂质排斥驱动的疏水性的一般分离。
