气候变化领域集成服务门户(CCPortal): Co-evolution of interacting proteins through non-contacting and non-specific mutations

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DOI	10.1038/s41559-022-01688-0
	Co-evolution of interacting proteins through non-contacting and non-specific mutations
	Ding D.; Green A.G.; Wang B.; Lite T.-L.V.; Weinstein E.N.; Marks D.S.; Laub M.T.
发表日期	2022
ISSN	2397-334X
起始页码	590
结束页码	603
卷号	6 期号:5
英文摘要	Proteins often accumulate neutral mutations that do not affect current functions but can profoundly influence future mutational possibilities and functions. Understanding such hidden potential has major implications for protein design and evolutionary forecasting but has been limited by a lack of systematic efforts to identify potentiating mutations. Here, through the comprehensive analysis of a bacterial toxin–antitoxin system, we identified all possible single substitutions in the toxin that enable it to tolerate otherwise interface-disrupting mutations in its antitoxin. Strikingly, the majority of enabling mutations in the toxin do not contact and promote tolerance non-specifically to many different antitoxin mutations, despite covariation in homologues occurring primarily between specific pairs of contacting residues across the interface. In addition, the enabling mutations we identified expand future mutational paths that both maintain old toxin–antitoxin interactions and form new ones. These non-specific mutations are missed by widely used covariation and machine learning methods. Identifying such enabling mutations will be critical for ensuring continued binding of therapeutically relevant proteins, such as antibodies, aimed at evolving targets. ? 2022, The Author(s), under exclusive licence to Springer Nature Limited.
语种	英语
scopus关键词	antitoxin; bacterial protein; bacterial toxin; amino acid sequence; chemistry; genetics; metabolism; mutation; Amino Acid Sequence; Antitoxins; Bacterial Proteins; Bacterial Toxins; Mutation
来源期刊	Nature Ecology & Evolution
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/257070
作者单位	Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, United States; Department of Systems Biology, Harvard Medical School, Boston, MA, United States; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, United States; Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX, United States; Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA, United States; Program in Biophysics, Harvard University, Boston, MA, United States; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, United States
推荐引用方式 GB/T 7714	Ding D.,Green A.G.,Wang B.,et al. Co-evolution of interacting proteins through non-contacting and non-specific mutations[J],2022,6(5).
APA	Ding D..,Green A.G..,Wang B..,Lite T.-L.V..,Weinstein E.N..,...&Laub M.T..(2022).Co-evolution of interacting proteins through non-contacting and non-specific mutations.Nature Ecology & Evolution,6(5).
MLA	Ding D.,et al."Co-evolution of interacting proteins through non-contacting and non-specific mutations".Nature Ecology & Evolution 6.5(2022).