Department of Plant Molecular Biology, Faculty of Biology and Medicine, University of Lausanne, CH-1015 Lausanne, Switzerland.
Department of Biomolecular Sciences, The Weizmann Institute of Science, 7610001 Rehovot, Israel.
Proc Natl Acad Sci U S A. 2021 May 25;118(21). doi: 10.1073/pnas.2020885118.
Across the Tree of Life (ToL), the complexity of proteomes varies widely. Our systematic analysis depicts that from the simplest archaea to mammals, the total number of proteins per proteome expanded ∼200-fold. Individual proteins also became larger, and multidomain proteins expanded ∼50-fold. Apart from duplication and divergence of existing proteins, completely new proteins were born. Along the ToL, the number of different folds expanded ∼5-fold and fold combinations ∼20-fold. Proteins prone to misfolding and aggregation, such as repeat and beta-rich proteins, proliferated ∼600-fold and, accordingly, proteins predicted as aggregation-prone became 6-fold more frequent in mammalian compared with bacterial proteomes. To control the quality of these expanding proteomes, core chaperones, ranging from heat shock proteins 20 (HSP20s) that prevent aggregation to HSP60, HSP70, HSP90, and HSP100 acting as adenosine triphosphate (ATP)-fueled unfolding and refolding machines, also evolved. However, these core chaperones were already available in prokaryotes, and they comprise ∼0.3% of all genes from archaea to mammals. This challenge-roughly the same number of core chaperones supporting a massive expansion of proteomes-was met by 1) elevation of messenger RNA (mRNA) and protein abundances of the ancient generalist core chaperones in the cell, and 2) continuous emergence of new substrate-binding and nucleotide-exchange factor cochaperones that function cooperatively with core chaperones as a network.
在生命之树上，蛋白质组的复杂性差异很大。我们的系统分析表明，从最简单的古菌到哺乳动物，每个蛋白质组的蛋白质总数扩大了约 200 倍。单个蛋白质也变得更大，多结构域蛋白质扩大了约 50 倍。除了现有蛋白质的复制和分化外，还诞生了全新的蛋白质。沿着生命之树，不同折叠的数量扩大了约 5 倍，折叠组合扩大了约 20 倍。容易错误折叠和聚集的蛋白质，如重复和富含β的蛋白质，增殖了约 600 倍，相应地，与细菌蛋白质组相比，预测为易聚集的蛋白质在哺乳动物蛋白质组中出现的频率增加了 6 倍。为了控制这些不断扩大的蛋白质组的质量，核心伴侣蛋白也随之进化，从防止聚集的热休克蛋白 20（HSP20）到 HSP60、HSP70、HSP90 和 HSP100，它们充当着三磷酸腺苷（ATP）驱动的展开和重折叠机器。然而，这些核心伴侣蛋白在原核生物中已经存在，它们占从古菌到哺乳动物所有基因的约 0.3%。为了应对这一挑战——大约需要相同数量的核心伴侣蛋白来支持蛋白质组的大规模扩张——采取了以下两种策略：1）提高细胞内古老通用核心伴侣蛋白的信使 RNA（mRNA）和蛋白质丰度，2）不断涌现新的底物结合和核苷酸交换因子共伴侣蛋白，它们与核心伴侣蛋白一起作为一个网络协同作用。
