气候变化领域集成服务门户(CCPortal): Consensus sequence design as a general strategy to create hyperstable; biologically active proteins

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DOI	10.1073/pnas.1816707116
	Consensus sequence design as a general strategy to create hyperstable; biologically active proteins
	Sternke M.; Tripp K.W.; Barrick D.
发表日期	2019
ISSN	0027-8424
起始页码	11275
结束页码	11284
卷号	166 期号:23
英文摘要	Consensus sequence design offers a promising strategy for designing proteins of high stability while retaining biological activity since it draws upon an evolutionary history in which residues important for both stability and function are likely to be conserved. Although there have been several reports of successful consensus design of individual targets, it is unclear from these anecdotal studies how often this approach succeeds and how often it fails. Here, we attempt to assess generality by designing consensus sequences for a set of six protein families with a range of chain lengths, structures, and activities. We characterize the resulting consensus proteins for stability, structure, and biological activities in an unbiased way. We find that all six consensus proteins adopt cooperatively folded structures in solution. Strikingly, four of six of these consensus proteins show increased thermodynamic stability over naturally occurring homologs. Each consensus protein tested for function maintained at least partial biological activity. Although peptide binding affinity by a consensus-designed SH3 is rather low, Km values for consensus enzymes are similar to values from extant homologs. Although consensus enzymes are slower than extant homologs at low temperature, they are faster than some thermophilic enzymes at high temperature. An analysis of sequence properties shows consensus proteins to be enriched in charged residues, and rarified in uncharged polar residues. Sequence differences between consensus and extant homologs are predominantly located at weakly conserved surface residues, highlighting the importance of these residues in the success of the consensus strategy. © 2019 National Academy of Sciences. All rights reserved.
英文关键词	Consensus sequence; Protein design; Protein stability
语种	英语
scopus关键词	article; binding affinity; biological activity; consensus sequence; high temperature; low temperature; protein family; protein function; protein stability; consensus sequence; genetics; temperature; thermodynamics; protein; Consensus Sequence; Proteins; Temperature; Thermodynamics
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/160427
作者单位	Sternke, M., T.C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, MD 21218, United States; Tripp, K.W., T.C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, MD 21218, United States; Barrick, D., T.C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, MD 21218, United States
推荐引用方式 GB/T 7714	Sternke M.,Tripp K.W.,Barrick D.. Consensus sequence design as a general strategy to create hyperstable; biologically active proteins[J],2019,166(23).
APA	Sternke M.,Tripp K.W.,&Barrick D..(2019).Consensus sequence design as a general strategy to create hyperstable; biologically active proteins.Proceedings of the National Academy of Sciences of the United States of America,166(23).
MLA	Sternke M.,et al."Consensus sequence design as a general strategy to create hyperstable; biologically active proteins".Proceedings of the National Academy of Sciences of the United States of America 166.23(2019).