The relationship between membrane proteins and the lipid constituents of the membrane bilayer depends on finely-tuned atomic interactions, which itself depends on the precise distribution of amino acids within the 3D structure of the protein. In this regard, tryptophan (Trp), one of the least abundant amino acids, is found at higher levels in transmembrane proteins where it likely plays a role in helping anchor them to the membrane. We now re-evaluate Trp distribution in membrane proteins using all known proteins in the Swiss-Prot database and confirm that it is somewhat higher (∼1.7%) than in soluble proteins (∼1.0%), but not as high as in a well-quoted study (∼3.1%). However, the resident endoplasmic reticulum membrane protein, ceramide synthase (CerS), contains a higher abundance of Trp (3.4%). In the case of CerS which contain a Hox-like domain, the Trp residues are asymmetrically distributed throughout the protein with a bias towards the lumenal side of the endoplasmic reticulum membrane. Mutation of these residues, even to other hydrophobic amino acids, leads to loss of activity, expression and/or N-glycosylation. Moreover, 5 of the 10 most conserved amino acids in the CerS are Trp, and site-directed mutagenesis of numerous conserved Trp residues to alanine had distinct effects. Our data is consistent with other studies suggesting that Trp plays critical roles not only in membrane anchoring of transmembrane proteins but also in their activity and function.

中文翻译：

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根据对 Swiss-Prot 数据库中的所有膜蛋白的分析，神经酰胺合酶中色氨酸残基的异常丰度。


膜蛋白与膜双层脂质成分之间的关系取决于精细调整的原子相互作用，而原子相互作用本身取决于氨基酸在蛋白质 3D 结构中的精确分布。在这方面，色氨酸 （Trp） 是丰度最低的氨基酸之一，在跨膜蛋白中含量较高，它可能在帮助它们锚定到膜上发挥作用。我们现在使用 Swiss-Prot 数据库中的所有已知蛋白质重新评估膜蛋白中的 Trp 分布，并确认它略高于可溶性蛋白 （∼1.7%） （∼1.0%），但不如引用良好的研究 （∼3.1%） 高。然而，常驻内质网膜蛋白神经酰胺合酶 （CerS） 含有较高丰度的 Trp （3.4%）。在包含 Hox 样结构域的 CerS 的情况下，Trp 残基不对称分布在整个蛋白质中，偏向于内质网膜的管腔侧。这些残基的突变，甚至突变为其他疏水性氨基酸，都会导致活性、表达和/或 N-糖基化的丧失。此外，CerS 中 10 种最保守的氨基酸中有 5 种是 Trp，许多保守的 Trp 残基向丙氨酸的定点诱变具有明显的效果。我们的数据与其他研究一致，表明 Trp 不仅在跨膜蛋白的膜锚定中起关键作用，而且在其活性和功能中也起关键作用。