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DOI | 10.1126/science.aax8780 |
Computational design of a modular protein sense-response system | |
Glasgow, Anum A.1; Huang, Yao-Ming1,8; Mandell, Daniel J.1,2,9; Thompson, Michael1; Ritterson, Ryan1,10; Loshbaugh, Amanda L.1,3; Pellegrino, Jenna1,3; Krivacic, Cody1,4; Pache, Roland A.1,11; Barlow, Kyle A.1,2,12; Ollikainen, Noah1,2; Jeon, Deborah1; Kelly, Mark J. S.5; Fraser, James S.1,3,6; Kortemme, Tanja1,2,3,4,6,7 | |
2019-11-22 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2019 |
卷号 | 366期号:6468页码:1024-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Denmark |
英文摘要 | Sensing and responding to signals is a fundamental ability of living systems, but despite substantial progress in the computational design of new protein structures, there is no general approach for engineering arbitrary new protein sensors. Here, we describe a generalizable computational strategy for designing sensor-actuator proteins by building binding sites de novo into heterodimeric protein-protein interfaces and coupling ligand sensing to modular actuation through split reporters. Using this approach, we designed protein sensors that respond to farnesyl pyrophosphate, a metabolic intermediate in the production of valuable compounds. The sensors are functional in vitro and in cells, and the crystal structure of the engineered binding site closely matches the design model. Our computational design strategy opens broad avenues to link biological outputs to new signals. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000498849000047 |
WOS关键词 | HIGH-AFFINITY ; DOMAIN ; STABILITY ; COMPLEX ; MUTAGENESIS ; VALIDATION ; STRATEGIES ; PREDICTION ; ACCURACY ; CRYSTALS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/226251 |
专题 | 环境与发展全球科技态势 |
作者单位 | 1.Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA; 2.Univ Calif San Francisco, Bioinformat Grad Program, San Francisco, CA 94143 USA; 3.Univ Calif San Francisco, Biophys Grad Program, San Francisco, CA 94143 USA; 4.Univ Calif San Francisco, UC Berkeley UCSF Grad Program Bioengn, San Francisco, CA 94143 USA; 5.Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA; 6.Univ Calif San Francisco, Quantitat Biosci Inst, San Francisco, CA 94143 USA; 7.Chan Zuckerberg Biohub, San Francisco, CA 94158 USA; 8.23andMe Inc, Therapeut, San Francisco, CA USA; 9.GRO Biosci, Boston, MA USA; 10.Gryphon Sci LLC, Takoma Pk, MA USA; 11.Novozymes AS, Biologiens Vej 2, DK-2800 Lyngby, Denmark; 12.Adimab LLC, Palo Alto, CA USA |
推荐引用方式 GB/T 7714 | Glasgow, Anum A.,Huang, Yao-Ming,Mandell, Daniel J.,et al. Computational design of a modular protein sense-response system[J]. SCIENCE,2019,366(6468):1024-+. |
APA | Glasgow, Anum A..,Huang, Yao-Ming.,Mandell, Daniel J..,Thompson, Michael.,Ritterson, Ryan.,...&Kortemme, Tanja.(2019).Computational design of a modular protein sense-response system.SCIENCE,366(6468),1024-+. |
MLA | Glasgow, Anum A.,et al."Computational design of a modular protein sense-response system".SCIENCE 366.6468(2019):1024-+. |
条目包含的文件 | 条目无相关文件。 |
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