气候变化领域集成服务门户(CCPortal): De novo design of protein logic gates

CCPortal

DOI	10.1126/science.aay2790
	De novo design of protein logic gates
	Chen Z.; Kibler R.D.; Hunt A.; Busch F.; Pearl J.; Jia M.; VanAernum Z.L.; Wicky B.I.M.; Dods G.; Liao H.; Wilken M.S.; Ciarlo C.; Green S.; El-Samad H.; Stamatoyannopoulos J.; Wysocki V.H.; Jewett M.C.; Boyken S.E.; Baker D.
发表日期	2020
ISSN	0036-8075
卷号	368 期号:6486
英文摘要	The design of modular protein logic for regulating protein function at the posttranscriptional level is a challenge for synthetic biology. Here, we describe the design of two-input AND, OR, NAND, NOR, XNOR, and NOT gates built from de novo-designed proteins. These gates regulate the association of arbitrary protein units ranging from split enzymes to transcriptional machinery in vitro, in yeast and in primary human T cells, where they control the expression of the TIM3 gene related to T cell exhaustion. Designed binding interaction cooperativity, confirmed by native mass spectrometry, makes the gates largely insensitive to stoichiometric imbalances in the inputs, and the modularity of the approach enables ready extension to three-input OR, AND, and disjunctive normal form gates. The modularity and cooperativity of the control elements, coupled with the ability to de novo design an essentially unlimited number of protein components, should enable the design of sophisticated posttranslational control logic over a wide range of biological functions. © 2020 American Association for the Advancement of Science. All rights reserved.
关键词	cell design method gene expression genetic analysis protein activation domain Article binding affinity circular dichroism controlled study de novo design design DNA binding motif enzyme activity genetic transcription human human cell hydrogen bond hydrophobicity mass spectrometry native mass spectrometry nonhuman priority journal protein protein interaction protein structure RNA translation stoichiometry thermodynamics two hybrid system X ray crystallography chemistry genetics logic metabolism protein analysis protein engineering protein processing synthetic biology T lymphocyte yeast HAVCR2 protein, human hepatitis A virus cellular receptor 2 Hepatitis A Virus Cellular Receptor 2 Humans Logic Mass Spectrometry Protein Engineering Protein Interaction Maps Protein Processing, Post-Translational Synthetic Biology T-Lymphocytes Transcription, Genetic Yeasts
语种	英语
来源机构	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/133584
推荐引用方式 GB/T 7714	Chen Z.,Kibler R.D.,Hunt A.,et al. De novo design of protein logic gates[J]. Science,2020,368(6486).
APA	Chen Z..,Kibler R.D..,Hunt A..,Busch F..,Pearl J..,...&Baker D..(2020).De novo design of protein logic gates.,368(6486).
MLA	Chen Z.,et al."De novo design of protein logic gates".368.6486(2020).