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Bioinspired Design of Artificial Signaling Systems
[Image: see text] Natural systems use weak interactions and avidity effects to give biological systems high specificity and signal-to-noise ratios. Here we describe design principles for engineering fusion proteins that target therapeutic fusion proteins to membrane-bound signaling receptors by firs...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9851155/ https://www.ncbi.nlm.nih.gov/pubmed/35984429 http://dx.doi.org/10.1021/acs.biochem.2c00368 |
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author | Way, Jeffrey C. Burrill, Devin R. Silver, Pamela A. |
author_facet | Way, Jeffrey C. Burrill, Devin R. Silver, Pamela A. |
author_sort | Way, Jeffrey C. |
collection | PubMed |
description | [Image: see text] Natural systems use weak interactions and avidity effects to give biological systems high specificity and signal-to-noise ratios. Here we describe design principles for engineering fusion proteins that target therapeutic fusion proteins to membrane-bound signaling receptors by first binding to designer-chosen co-receptors on the same cell surface. The key design elements are separate protein modules, one that has no signaling activity and binds to a cell surface receptor with high affinity and a second that binds to a receptor with low or moderate affinity and carries out a desired signaling or inhibitory activity. These principles are inspired by natural cytokines such as CNTF, IL-2, and IL-4 that bind strongly to nonsignaling receptors and then signal through low-affinity receptors. Such designs take advantage of the fact that when a protein is anchored to a cell membrane, its local concentration is extremely high with respect to those of other membrane proteins, so a second-step, low-affinity binding event is favored. Protein engineers have used these principles to design treatments for cancer, anemia, hypoxia, and HIV infection. |
format | Online Article Text |
id | pubmed-9851155 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-98511552023-08-19 Bioinspired Design of Artificial Signaling Systems Way, Jeffrey C. Burrill, Devin R. Silver, Pamela A. Biochemistry [Image: see text] Natural systems use weak interactions and avidity effects to give biological systems high specificity and signal-to-noise ratios. Here we describe design principles for engineering fusion proteins that target therapeutic fusion proteins to membrane-bound signaling receptors by first binding to designer-chosen co-receptors on the same cell surface. The key design elements are separate protein modules, one that has no signaling activity and binds to a cell surface receptor with high affinity and a second that binds to a receptor with low or moderate affinity and carries out a desired signaling or inhibitory activity. These principles are inspired by natural cytokines such as CNTF, IL-2, and IL-4 that bind strongly to nonsignaling receptors and then signal through low-affinity receptors. Such designs take advantage of the fact that when a protein is anchored to a cell membrane, its local concentration is extremely high with respect to those of other membrane proteins, so a second-step, low-affinity binding event is favored. Protein engineers have used these principles to design treatments for cancer, anemia, hypoxia, and HIV infection. American Chemical Society 2022-08-19 /pmc/articles/PMC9851155/ /pubmed/35984429 http://dx.doi.org/10.1021/acs.biochem.2c00368 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Way, Jeffrey C. Burrill, Devin R. Silver, Pamela A. Bioinspired Design of Artificial Signaling Systems |
title | Bioinspired
Design of Artificial Signaling Systems |
title_full | Bioinspired
Design of Artificial Signaling Systems |
title_fullStr | Bioinspired
Design of Artificial Signaling Systems |
title_full_unstemmed | Bioinspired
Design of Artificial Signaling Systems |
title_short | Bioinspired
Design of Artificial Signaling Systems |
title_sort | bioinspired
design of artificial signaling systems |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9851155/ https://www.ncbi.nlm.nih.gov/pubmed/35984429 http://dx.doi.org/10.1021/acs.biochem.2c00368 |
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