دورية أكاديمية
De novo design of protein logic gates.
| العنوان: | De novo design of protein logic gates. |
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| المؤلفون: | Chen Z; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA., Kibler RD; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA., Hunt A; Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208, USA., Busch F; Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA.; Resource for Native Mass Spectrometry Guided Structural Biology, The Ohio State University, Columbus, OH 43210, USA., Pearl J; Altius Institute for Biomedical Sciences, Seattle, WA 98195, USA., Jia M; Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA.; Resource for Native Mass Spectrometry Guided Structural Biology, The Ohio State University, Columbus, OH 43210, USA., VanAernum ZL; Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA.; Resource for Native Mass Spectrometry Guided Structural Biology, The Ohio State University, Columbus, OH 43210, USA., Wicky BIM; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA., Dods G; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA., Liao H; Altius Institute for Biomedical Sciences, Seattle, WA 98195, USA., Wilken MS; Altius Institute for Biomedical Sciences, Seattle, WA 98195, USA., Ciarlo C; Altius Institute for Biomedical Sciences, Seattle, WA 98195, USA., Green S; Altius Institute for Biomedical Sciences, Seattle, WA 98195, USA., El-Samad H; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.; Chan-Zuckerberg Biohub, San Francisco, CA 94158, USA., Stamatoyannopoulos J; Altius Institute for Biomedical Sciences, Seattle, WA 98195, USA.; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.; Department of Medicine, Division of Oncology, University of Washington, Seattle, WA 98109, USA., Wysocki VH; Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA.; Resource for Native Mass Spectrometry Guided Structural Biology, The Ohio State University, Columbus, OH 43210, USA., Jewett MC; Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208, USA.; Chemistry of Life Processes Institute, Northwestern University, Evanston, IL 60208, USA.; Center for Synthetic Biology, Northwestern University, Evanston, IL 60208, USA., Boyken SE; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA., Baker D; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. dabaker@uw.edu.; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. |
| المصدر: | Science (New York, N.Y.) [Science] 2020 Apr 03; Vol. 368 (6486), pp. 78-84. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print Cited Medium: Internet ISSN: 1095-9203 (Electronic) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Original Publication: New York, N.Y. : [s.n.] 1880- |
| مواضيع طبية MeSH: | Protein Engineering* , Protein Interaction Maps* , Protein Processing, Post-Translational*, Hepatitis A Virus Cellular Receptor 2/*chemistry, Hepatitis A Virus Cellular Receptor 2/genetics ; Humans ; Logic ; Mass Spectrometry ; Synthetic Biology ; T-Lymphocytes/metabolism ; Transcription, Genetic ; Yeasts/metabolism |
| مستخلص: | 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. (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.) |
| التعليقات: | Comment in: Nat Methods. 2020 Jun;17(6):565. (PMID: 32499622) |
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| معلومات مُعتمدة: | P41 GM103533 United States GM NIGMS NIH HHS; P30 GM124169 United States GM NIGMS NIH HHS; United States HHMI Howard Hughes Medical Institute; S10 OD018483 United States OD NIH HHS; P01 CA092584 United States CA NCI NIH HHS; P41 GM128577 United States GM NIGMS NIH HHS; R33 HL120752 United States HL NHLBI NIH HHS |
| المشرفين على المادة: | 0 (HAVCR2 protein, human) 0 (Hepatitis A Virus Cellular Receptor 2) |
| تواريخ الأحداث: | Date Created: 20200404 Date Completed: 20200420 Latest Revision: 20201003 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC7397813 |
| DOI: | 10.1126/science.aay2790 |
| PMID: | 32241946 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1095-9203 |
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| DOI: | 10.1126/science.aay2790 |