{"abstract":[{"lang":"eng","text":"In nature, proteins that switch between two conformations in response to environmental stimuli structurally transduce biochemical information in a manner analogous to how transistors control information flow in computing devices. Designing proteins with two distinct but fully structured conformations is a challenge for protein design as it requires sculpting an energy landscape with two distinct minima. Here we describe the design of “hinge” proteins that populate one designed state in the absence of ligand and a second designed state in the presence of ligand. X-ray crystallography, electron microscopy, double electron-electron resonance spectroscopy, and binding measurements demonstrate that despite the significant structural differences the two states are designed with atomic level accuracy and that the conformational and binding equilibria are closely coupled."}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","quality_controlled":"1","publication_status":"published","status":"public","publication_identifier":{"issn":["0036-8075"],"eissn":["1095-9203"]},"extern":"1","article_type":"original","year":"2023","article_processing_charge":"No","external_id":{"pmid":["37590357"]},"page":"754-760","publication":"Science","language":[{"iso":"eng"}],"pmid":1,"day":"17","author":[{"id":"dfec9381-4341-11ee-8fd8-faa02bba7d62","last_name":"Praetorius","first_name":"Florian M","full_name":"Praetorius, Florian M"},{"full_name":"Leung, Philip J. Y.","first_name":"Philip J. Y.","last_name":"Leung"},{"full_name":"Tessmer, Maxx H.","last_name":"Tessmer","first_name":"Maxx H."},{"full_name":"Broerman, Adam","first_name":"Adam","last_name":"Broerman"},{"first_name":"Cullen","last_name":"Demakis","full_name":"Demakis, Cullen"},{"last_name":"Dishman","first_name":"Acacia F.","full_name":"Dishman, Acacia F."},{"full_name":"Pillai, Arvind","first_name":"Arvind","last_name":"Pillai"},{"full_name":"Idris, Abbas","last_name":"Idris","first_name":"Abbas"},{"full_name":"Juergens, David","last_name":"Juergens","first_name":"David"},{"full_name":"Dauparas, Justas","first_name":"Justas","last_name":"Dauparas"},{"first_name":"Xinting","last_name":"Li","full_name":"Li, Xinting"},{"first_name":"Paul M.","last_name":"Levine","full_name":"Levine, Paul M."},{"full_name":"Lamb, Mila","last_name":"Lamb","first_name":"Mila"},{"full_name":"Ballard, Ryanne K.","last_name":"Ballard","first_name":"Ryanne K."},{"first_name":"Stacey R.","last_name":"Gerben","full_name":"Gerben, Stacey R."},{"first_name":"Hannah","last_name":"Nguyen","full_name":"Nguyen, Hannah"},{"last_name":"Kang","first_name":"Alex","full_name":"Kang, Alex"},{"full_name":"Sankaran, Banumathi","last_name":"Sankaran","first_name":"Banumathi"},{"full_name":"Bera, Asim K.","last_name":"Bera","first_name":"Asim K."},{"first_name":"Brian F.","last_name":"Volkman","full_name":"Volkman, Brian F."},{"last_name":"Nivala","first_name":"Jeff","full_name":"Nivala, Jeff"},{"full_name":"Stoll, Stefan","first_name":"Stefan","last_name":"Stoll"},{"first_name":"David","last_name":"Baker","full_name":"Baker, David"}],"publisher":"American Association for the Advancement of Science","oa_version":"None","doi":"10.1126/science.adg7731","date_updated":"2023-11-07T12:42:09Z","type":"journal_article","date_created":"2023-09-06T12:04:23Z","intvolume":"       381","month":"08","date_published":"2023-08-17T00:00:00Z","scopus_import":"1","title":"Design of stimulus-responsive two-state hinge proteins","volume":381,"_id":"14281","citation":{"chicago":"Praetorius, Florian M, Philip J. Y. Leung, Maxx H. Tessmer, Adam Broerman, Cullen Demakis, Acacia F. Dishman, Arvind Pillai, et al. “Design of Stimulus-Responsive Two-State Hinge Proteins.” <i>Science</i>. American Association for the Advancement of Science, 2023. <a href=\"https://doi.org/10.1126/science.adg7731\">https://doi.org/10.1126/science.adg7731</a>.","apa":"Praetorius, F. M., Leung, P. J. Y., Tessmer, M. H., Broerman, A., Demakis, C., Dishman, A. F., … Baker, D. (2023). Design of stimulus-responsive two-state hinge proteins. <i>Science</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/science.adg7731\">https://doi.org/10.1126/science.adg7731</a>","short":"F.M. Praetorius, P.J.Y. Leung, M.H. Tessmer, A. Broerman, C. Demakis, A.F. Dishman, A. Pillai, A. Idris, D. Juergens, J. Dauparas, X. Li, P.M. Levine, M. Lamb, R.K. Ballard, S.R. Gerben, H. Nguyen, A. Kang, B. Sankaran, A.K. Bera, B.F. Volkman, J. Nivala, S. Stoll, D. Baker, Science 381 (2023) 754–760.","ista":"Praetorius FM, Leung PJY, Tessmer MH, Broerman A, Demakis C, Dishman AF, Pillai A, Idris A, Juergens D, Dauparas J, Li X, Levine PM, Lamb M, Ballard RK, Gerben SR, Nguyen H, Kang A, Sankaran B, Bera AK, Volkman BF, Nivala J, Stoll S, Baker D. 2023. Design of stimulus-responsive two-state hinge proteins. Science. 381(6659), 754–760.","ieee":"F. M. Praetorius <i>et al.</i>, “Design of stimulus-responsive two-state hinge proteins,” <i>Science</i>, vol. 381, no. 6659. American Association for the Advancement of Science, pp. 754–760, 2023.","mla":"Praetorius, Florian M., et al. “Design of Stimulus-Responsive Two-State Hinge Proteins.” <i>Science</i>, vol. 381, no. 6659, American Association for the Advancement of Science, 2023, pp. 754–60, doi:<a href=\"https://doi.org/10.1126/science.adg7731\">10.1126/science.adg7731</a>.","ama":"Praetorius FM, Leung PJY, Tessmer MH, et al. Design of stimulus-responsive two-state hinge proteins. <i>Science</i>. 2023;381(6659):754-760. doi:<a href=\"https://doi.org/10.1126/science.adg7731\">10.1126/science.adg7731</a>"},"issue":"6659"}