Department of Biophysics, Molecular Biology and Bioinformatics, University of Calcutta, 92 Acharya Prafulla Chandra Road, Kolkata 700009, India.
Structure. 2018 Jun 5;26(6):869-878.e3. doi: 10.1016/j.str.2018.04.015. Epub 2018 May 24.
To find additional structural constraints (besides disordered segments) that regulate protein half-life in the cell, we herein assess the influence of native topology of monomeric and sequestration of oligomeric proteins into multimeric complexes in yeast, human, and mouse. Native topology acts as a molecular marker of globular protein's mechanical resistance and consequently captures their half-life variations on genome scale. Sequestration into multimeric complexes elongates oligomeric protein half-life in the cell, presumably by burying ubiquitinoylation sites and disordered segments required for proteasomal recognition. The latter effect is stronger for proteins associated with multiple complexes and for those binding early during complex self-assembly, including proteins that oligomerize with large proportions of surface buried. After gene duplication, diversification of topology and sequestration into non-identical sets of complexes alter half-lives of paralogous proteins during the course of evolution. Thus, native topology and sequestration into multimeric complexes reflect designing principles of proteins to regulate their half-lives.
为了在细胞内寻找调节蛋白质半衰期的其他结构限制因素（除了无规则片段），我们在此评估了单体的天然拓扑结构和寡聚蛋白在酵母、人类和小鼠中隔离到多聚体复合物的影响。天然拓扑结构作为球状蛋白质机械抗性的分子标志物，因此可以在基因组范围内捕获它们的半衰期变化。隔离到多聚体复合物中会延长细胞内寡聚蛋白的半衰期，这可能是通过掩埋泛素化位点和多蛋白体识别所需的无规则片段。对于与多个复合物相关的蛋白质以及在复合物自组装早期结合的蛋白质，这种效应更强，包括与大比例表面掩埋的蛋白质形成寡聚体的蛋白质。在基因复制后，拓扑结构的多样化和隔离到非同源复合物集改变了进化过程中同源蛋白质的半衰期。因此，天然拓扑结构和隔离到多聚体复合物反映了蛋白质设计原则，以调节它们的半衰期。
