Loos Maria S, Ramakrishnan Reshmi, Vranken Wim, Tsirigotaki Alexandra, Tsare Evrydiki-Pandora, Zorzini Valentina, Geyter Jozefien De, Yuan Biao, Tsamardinos Ioannis, Klappa Maria, Schymkowitz Joost, Rousseau Frederic, Karamanou Spyridoula, Economou Anastassios
Department of Microbiology and Immunology, Laboratory of Molecular Bacteriology, Rega Institute, KU Leuven, Leuven, Belgium.
VIB Switch Laboratory, Department for Cellular and Molecular Medicine, VIB-KU Leuven Center for Brain & Disease Research, KU Leuven, Leuven, Belgium.
Front Microbiol. 2019 Jul 24;10:1670. doi: 10.3389/fmicb.2019.01670. eCollection 2019.
Cellular proteomes are distributed in multiple compartments: on DNA, ribosomes, on and inside membranes, or they become secreted. Structural properties that allow polypeptides to occupy subcellular niches, particularly to after crossing membranes, remain unclear. We compared intrinsic and extrinsic features in cytoplasmic and secreted polypeptides of the K-12 proteome. Structural features between the cytoplasmome and secretome are sharply distinct, such that a signal peptide-agnostic machine learning tool distinguishes cytoplasmic from secreted proteins with 95.5% success. Cytoplasmic polypeptides are enriched in aliphatic, aromatic, charged and hydrophobic residues, unique folds and higher early folding propensities. Secretory polypeptides are enriched in polar/small amino acids, β folds, have higher backbone dynamics, higher disorder and contact order and are more often intrinsically disordered. These non-random distributions and experimental evidence imply that evolutionary pressure selected enhanced secretome flexibility, slow folding and looser structures, placing the secretome in a distinct protein class. These adaptations protect the secretome from premature folding during its cytoplasmic transit, optimize its lipid bilayer crossing and allowed it to acquire cell envelope specific chemistries. The latter may favor promiscuous multi-ligand binding, sensing of stress and cell envelope structure changes. In conclusion, enhanced flexibility, slow folding, looser structures and unique folds differentiate the secretome from the cytoplasmome. These findings have wide implications on the structural diversity and evolution of modern proteomes and the protein folding problem.
存在于DNA、核糖体上，存在于膜上及膜内，或者被分泌出去。多肽占据亚细胞特定位置的结构特性，尤其是在穿过膜之后的特性，仍不清楚。我们比较了K - 12蛋白质组中细胞质多肽和分泌多肽的内在与外在特征。细胞质蛋白质组和分泌蛋白质组之间的结构特征截然不同，以至于一种不依赖信号肽的机器学习工具区分细胞质蛋白和分泌蛋白的成功率达到95.5%。细胞质多肽富含脂肪族、芳香族、带电荷和疏水残基，具有独特的折叠方式和更高的早期折叠倾向。分泌多肽富含极性/小氨基酸、β折叠，具有更高的主链动力学、更高的无序性和接触序，并且更常为内在无序。这些非随机分布和实验证据表明，进化压力选择了增强的分泌蛋白质组灵活性、缓慢折叠和更松散的结构，使分泌蛋白质组属于一种独特的蛋白质类别。这些适应性变化保护分泌蛋白质组在细胞质转运过程中不提前折叠，优化其穿越脂质双层的过程，并使其能够获得细胞被膜特异性化学性质。后者可能有利于杂乱的多配体结合、应激感知和细胞被膜结构变化。总之，增强的灵活性、缓慢折叠、更松散的结构和独特的折叠方式使分泌蛋白质组区别于细胞质蛋白质组。这些发现对现代蛋白质组的结构多样性和进化以及蛋白质折叠问题具有广泛影响。
