globalchange  > 气候变化与战略
DOI: 10.1073/pnas.1816707116
论文题名:
Consensus sequence design as a general strategy to create hyperstable; biologically active proteins
作者: Sternke M.; Tripp K.W.; Barrick D.
刊名: Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
出版年: 2019
卷: 166, 期:23
起始页码: 11275
结束页码: 11284
语种: 英语
英文关键词: Consensus sequence ; Protein design ; Protein stability
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
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.
Citation statistics:
资源类型: 期刊论文
标识符: http://119.78.100.158/handle/2HF3EXSE/163620
Appears in Collections:气候变化与战略

Files in This Item:

There are no files associated with this item.


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

Recommended Citation:
Sternke M.,Tripp K.W.,Barrick D.. Consensus sequence design as a general strategy to create hyperstable; biologically active proteins[J]. Proceedings of the National Academy of Sciences of the United States of America,2019-01-01,166(23)
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Sternke M.]'s Articles
[Tripp K.W.]'s Articles
[Barrick D.]'s Articles
百度学术
Similar articles in Baidu Scholar
[Sternke M.]'s Articles
[Tripp K.W.]'s Articles
[Barrick D.]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Sternke M.]‘s Articles
[Tripp K.W.]‘s Articles
[Barrick D.]‘s Articles
Related Copyright Policies
Null
收藏/分享
所有评论 (0)
暂无评论
 

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.