Systematic profiling of dominant ubiquitin variants reveals key functional nodes contributing to evolutionary selection.
Systematic profiling of dominant ubiquitin variants reveals key functional nodes contributing to evolutionary selection.
复制标题
对主要泛素变体的系统分析揭示了有助于进化选择的关键功能节点。
DOI：
10.1016/j.celrep.2023.113064
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发表时间：
2023
期刊：
影响因子：
8.8
通讯作者：
Mishra,Parul
中科院分区：
文献类型：
--
作者：
Padhy,AmritaArpita;Mavor,David;Sahoo,Subhashree;Bolon,DanielNA;Mishra,Parul
显性负突变可以帮助研究生物学机制和了解多功能蛋白的选择压力。然而，大多数研究都集中在隐性突变效应上，这种效应发生在缺乏第二个功能基因拷贝的情况下，这忽视了大多数真核生物基因组包含许多基因的多个拷贝的事实。我们已经确定了在泛素与野生型等位基因一起表达的所有可能的点突变中对酵母生长速率的显性影响。我们的研究结果揭示了400多个显性负突变，表明显性负效应对泛素的选择有相当大的贡献。单个泛素变异的细胞和生化分析表明，多泛素化细胞蛋白的不同积累和/或泛素变异与泛素连接酶的结合缺陷可以解释显性负作用。我们鉴定显性负突变的方法是通用的，可以应用于其他感兴趣的蛋白质。
Dominant-negative mutations can help to investigate the biological mechanisms and to understand the selective pressures for multifunctional proteins. However, most studies have focused on recessive mutant effects that occur in the absence of a second functional gene copy, which overlooks the fact that most eukaryotic genomes contain more than one copy of many genes. We have identified dominant effects on yeast growth rate among all possible point mutations in ubiquitin expressed alongside a wild-type allele. Our results reveal more than 400 dominant-negative mutations, indicating that dominant-negative effects make a sizable contribution to selection acting on ubiquitin. Cellular and biochemical analyses of individual ubiquitin variants show that dominant-negative effects are explained by varied accumulation of polyubiquitinated cellular proteins and/or defects in conjugation of ubiquitin variants to ubiquitin ligases. Our approach to identify dominant-negative mutations is general and can be applied to other proteins of interest.
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影响因子：
8.8
作者：
Mishra P;Flynn JM;Starr TN;Bolon DNA
通讯作者：
Bolon DNA
影响因子：
16.6
作者：
Finley D
通讯作者：
Finley D
影响因子：
7.7
作者：
David Mavor;Kyle A. Barlow;Samuel Thompson;B. Barad;Alain R. Bonny;Clinton L. Cario;Garrett Gaskins;Zairan Liu;Laura Deming;S. Axen;Elena L. Cáceres;Weilin Chen;A. Cuesta;Rachel E. Gate;E. Green;Kaitlin R Hulce;Weiyue Ji;L. Kenner;Bruk Mensa;L. Morinishi;Steven M. Moss;M. Mravic;Ryan K Muir;Stefan Niekamp;C. Nnadi;Eugene Palovcak;E. Poss;T. Ross;Eugenia C. Salcedo;Stephanie K. See;Meena Subramaniam;A. Wong;Jennifer Li;K. Thorn;S. Conchúir;Benjamin P. Roscoe;E. Chow;J. Derisi;T. Kortemme;Daniel N. A. Bolon;J. Fraser
通讯作者：
David Mavor;Kyle A. Barlow;Samuel Thompson;B. Barad;Alain R. Bonny;Clinton L. Cario;Garrett Gaskins;Zairan Liu;Laura Deming;S. Axen;Elena L. Cáceres;Weilin Chen;A. Cuesta;Rachel E. Gate;E. Green;Kaitlin R Hulce;Weiyue Ji;L. Kenner;Bruk Mensa;L. Morinishi;Steven M. Moss;M. Mravic;Ryan K Muir;Stefan Niekamp;C. Nnadi;Eugene Palovcak;E. Poss;T. Ross;Eugenia C. Salcedo;Stephanie K. See;Meena Subramaniam;A. Wong;Jennifer Li;K. Thorn;S. Conchúir;Benjamin P. Roscoe;E. Chow;J. Derisi;T. Kortemme;Daniel N. A. Bolon;J. Fraser
DOI：
10.1101/820068
发表时间：
2019-10
期刊：
Proceedings of the National Academy of Sciences
影响因子：
--
作者：
Jacob D. Mehlhoff;Frank W. Stearns;Dahlia Rohm;Buheng Wang;Erh-Yeh Tsou;Nisita Dutta;Meng-Hsuan Hsiao;Courtney E. Gonzalez;Alan F. Rubin;M. Ostermeier
通讯作者：
Jacob D. Mehlhoff;Frank W. Stearns;Dahlia Rohm;Buheng Wang;Erh-Yeh Tsou;Nisita Dutta;Meng-Hsuan Hsiao;Courtney E. Gonzalez;Alan F. Rubin;M. Ostermeier
影响因子：
16.6
作者：
Zecha J;Gabriel W;Spallek R;Chang YC;Mergner J;Wilhelm M;Bassermann F;Kuster B
通讯作者：
Kuster B