Division of Biological Sciences, Pacific Northwest National Laboratory, Richland, Washington, USA.
mBio. 2012 Nov 20;3(6):e00339-12. doi: 10.1128/mBio.00339-12.
Signal peptides are a cornerstone mechanism for cellular protein localization, yet until now experimental determination of signal peptides has come from only a narrow taxonomic sampling. As a result, the dominant view is that Sec-cleaved signal peptides in prokaryotes are defined by a canonical AxA motif. Although other residues are permitted in the motif, alanine is by far the most common. Here we broadly examine proteomics data to reveal the signal peptide sequences for 32 bacterial and archaeal organisms from nine phyla and demonstrate that this alanine preference is not universal. Discoveries include fundamentally distinct signal peptide motifs from Alphaproteobacteria, Spirochaetes, Thermotogae and Euryarchaeota. In these novel motifs, alanine is no longer the dominant residue but has been replaced in a different way for each taxon. Surprisingly, divergent motifs correlate with a proteome-wide reduction in alanine. Computational analyses of ~1,500 genomes reveal numerous major evolutionary clades which have replaced the canonical signal peptide sequence with novel motifs.
This article replaces a widely held general model with a more detailed model describing phylogenetically correlated variation in motifs for Sec secretion.
信号肽是细胞蛋白定位的基石机制，但到目前为止，信号肽的实验测定仅来自于狭窄的分类采样。因此，主要观点是原核生物中 Sec 切割的信号肽由典型的 AxA 基序定义。尽管该基序中允许其他残基，但丙氨酸是迄今为止最常见的。在这里，我们广泛检查蛋白质组学数据，以揭示来自九个门的 32 个细菌和古细菌生物体的信号肽序列，并证明这种丙氨酸偏好并非普遍存在。发现包括来自 Alpha 变形菌、螺旋体、热球菌和广古菌的基本不同的信号肽基序。在这些新的基序中，丙氨酸不再是主要残基，但每个分类群都以不同的方式取代。令人惊讶的是，不同的基序与整个蛋白质组中丙氨酸的减少相关。对~1500 个基因组的计算分析揭示了许多主要的进化分支，它们用新的基序取代了典型的信号肽序列。
本文用一个更详细的模型取代了一个广泛持有的一般模型，该模型描述了 Sec 分泌的基序在系统发育上相关的变异。
