Design of stimulus-responsive two-state hinge proteins. Science 2023 Aug 18;381(6659):754-760
Date
08/17/2023Pubmed ID
37590357Pubmed Central ID
PMC10697137DOI
10.1126/science.adg7731Scopus ID
2-s2.0-85168284894 (requires institutional sign-in at Scopus site) 7 CitationsAbstract
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.
Author List
Praetorius F, 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 DAuthors
Acacia Frances Dishman MD, PhD Postdoctoral Fellow in the Biochemistry department at Medical College of WisconsinBrian F. Volkman PhD Professor in the Biochemistry department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Crystallography, X-RayLigands
Protein Conformation
Protein Engineering
