Institute for Biochemistry and Molecular Biology, Zentrum für Biochemie und Molekulare Medizin (ZMBZ), Faculty of Medicine, Albert-Ludwigs-Universität Freiburg, Germany.
FEBS J. 2021 Dec;288(24):7002-7024. doi: 10.1111/febs.15845. Epub 2021 Jun 8.
The large abundance of small open reading frames (smORFs) in prokaryotic and eukaryotic genomes and the plethora of smORF-encoded small proteins became only apparent with the constant advancements in bioinformatic, genomic, proteomic, and biochemical tools. Small proteins are typically defined as proteins of < 50 amino acids in prokaryotes and of less than 100 amino acids in eukaryotes, and their importance for cell physiology and cellular adaptation is only beginning to emerge. In contrast to antimicrobial peptides, which are secreted by prokaryotic and eukaryotic cells for combatting pathogens and competitors, small proteins act within the producing cell mainly by stabilizing protein assemblies and by modifying the activity of larger proteins. Production of small proteins is frequently linked to stress conditions or environmental changes, and therefore, cells seem to use small proteins as intracellular modifiers for adjusting cell metabolism to different intra- and extracellular cues. However, the size of small proteins imposes a major challenge for the cellular machinery required for protein folding and intracellular trafficking and recent data indicate that small proteins can engage distinct trafficking pathways. In the current review, we describe the diversity of small proteins in prokaryotes and eukaryotes, highlight distinct and common features, and illustrate how they are handled by the protein trafficking machineries in prokaryotic and eukaryotic cells. Finally, we also discuss future topics of research on this fascinating but largely unexplored group of proteins.
大量的小开放阅读框（smORFs）存在于原核生物和真核生物基因组中，大量由 smORF 编码的小蛋白也变得显而易见，这要归功于生物信息学、基因组学、蛋白质组学和生物化学工具的不断进步。小蛋白通常被定义为长度小于 50 个氨基酸的原核生物蛋白和小于 100 个氨基酸的真核生物蛋白，它们对细胞生理学和细胞适应的重要性才刚刚开始显现。与抗菌肽不同，抗菌肽是由原核生物和真核生物细胞分泌的，用于对抗病原体和竞争者，而小蛋白主要在产生它们的细胞内发挥作用，通过稳定蛋白质组装和修饰更大的蛋白质的活性。小蛋白的产生通常与应激条件或环境变化有关，因此，细胞似乎将小蛋白用作细胞内调节剂，以调整细胞代谢以适应不同的细胞内和细胞外信号。然而，小蛋白的大小给蛋白质折叠和细胞内运输所需的细胞机制带来了重大挑战，最近的数据表明，小蛋白可以参与不同的运输途径。在这篇综述中，我们描述了原核生物和真核生物中小蛋白的多样性，强调了它们的独特和共同特征，并说明了它们如何被原核生物和真核生物细胞中的蛋白质运输机制处理。最后，我们还讨论了这个迷人但在很大程度上尚未被探索的蛋白质群的未来研究主题。
