Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
Nat Rev Mol Cell Biol. 2020 Jun;21(6):327-340. doi: 10.1038/s41580-020-0231-2. Epub 2020 Mar 31.
The ability of living systems to adapt to changing conditions originates from their capacity to change their molecular constitution. This is achieved by multiple mechanisms that modulate the quantitative composition and the diversity of the molecular inventory. Molecular diversification is particularly pronounced on the proteome level, at which multiple proteoforms derived from the same gene can in turn combinatorially form different protein complexes, thus expanding the repertoire of functional modules in the cell. The study of molecular and modular diversity and their involvement in responses to changing conditions has only recently become possible through the development of new 'omics'-based screening technologies. This Review explores our current knowledge of the mechanisms regulating functional diversification along the axis of gene expression, with a focus on the proteome and interactome. We explore the interdependence between different molecular levels and how this contributes to functional diversity. Finally, we highlight several recent techniques for studying molecular diversity, with specific focus on mass spectrometry-based analysis of the proteome and its organization into functional modules, and examine future directions for this rapidly growing field.
生物系统适应变化条件的能力源于其改变分子结构的能力。这是通过多种机制实现的，这些机制调节分子库存的定量组成和多样性。分子多样化在蛋白质组水平上尤为明显，同一基因衍生的多种蛋白质异构体可以组合形成不同的蛋白质复合物，从而扩展细胞中功能模块的 repertoire。只有最近通过开发新的基于“组学”的筛选技术，才有可能研究分子和模块多样性及其在应对变化条件中的作用。这篇综述探讨了我们目前对调节基因表达轴上功能多样化的机制的认识，重点是蛋白质组和相互作用组。我们探讨了不同分子水平之间的相互依存关系以及这如何有助于功能多样性。最后，我们强调了几种研究分子多样性的新技术，特别关注基于质谱的蛋白质组分析及其组织成功能模块，并探讨了这个快速发展领域的未来方向。
