8FIT

Multi-state design of two-state switchable hinge proteins

Summary for 8FIT

• Entry DOI: 10.2210/pdb8fit/pdb
• Descriptor: cs074A (2 entities in total)
• Functional Keywords: de novo protein, metamorphic proteins, switchable hinge proteins, protein dynamics
• Biological source: synthetic construct
• Total number of polymer chains: 4
• Total formula weight: 117462.40

Authors

Bera, A.K.,Praetorius, F.,Baker, D. (deposition date: 2022-12-16, release date: 2023-08-16, Last modification date: 2024-03-06)

Primary citation

Praetorius, F.,Leung, P.J.Y.,Tessmer, M.H.,Broerman, A.,Demakis, C.,Dishman, A.F.,Pillai, A.,Idris, A.,Juergens, D.,Dauparas, J.,Li, X.,Levine, P.M.,Lamb, M.,Ballard, R.K.,Gerben, S.R.,Nguyen, H.,Kang, A.,Sankaran, B.,Bera, A.K.,Volkman, B.F.,Nivala, J.,Stoll, S.,Baker, D.
Design of stimulus-responsive two-state hinge proteins.
Science, 381:754-760, 2023

PubMed Abstract: 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.

PubMed: 37590357
DOI: 10.1126/science.adg7731

Experimental method

X-RAY DIFFRACTION (2.75 Å)