8E6Y

NMR structure of Sa1_V90T at 30 degrees Celsius

Summary for 8E6Y

• Entry DOI: 10.2210/pdb8e6y/pdb
• NMR Information: BMRB: 51339
• Descriptor: Sa1_V90T_30C (1 entity in total)
• Functional Keywords: alpha-beta plait, structural protein
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 10602.31

Authors

Solomon, T.S.,Orban, J. (deposition date: 2022-08-23, release date: 2023-01-11, Last modification date: 2024-05-15)

Primary citation

Solomon, T.L.,He, Y.,Sari, N.,Chen, Y.,Gallagher, D.T.,Bryan, P.N.,Orban, J.
Reversible switching between two common protein folds in a designed system using only temperature.
Proc.Natl.Acad.Sci.USA, 120:e2215418120-e2215418120, 2023

PubMed Abstract: Naturally occurring metamorphic proteins have the ability to interconvert from one folded state to another through either a limited set of mutations or by way of a change in the local environment. Here, we show in a designed system that it is possible to switch reversibly between two of the most common monomeric folds employing only temperature changes. We demonstrate that a latent 3α state can be unmasked from an α/β-plait topology with a single V90T amino acid substitution, populating both forms simultaneously. The equilibrium between these two states exhibits temperature dependence, such that the 3α state is predominant (>90%) at 5 °C, while the α/β-plait fold is the major species (>90%) at 30 °C. We describe the structure and dynamics of these topologies, how mutational changes affect the temperature dependence, and the energetics and kinetics of interconversion. Additionally, we demonstrate how ligand-binding function can be tightly regulated by large amplitude changes in protein structure over a relatively narrow temperature range that is relevant to biology. The 3α/αβ switch thus represents a potentially useful approach for designing proteins that alter their fold topologies in response to environmental triggers. It may also serve as a model for computational studies of temperature-dependent protein stability and fold switching.

PubMed: 36669114
DOI: 10.1073/pnas.2215418120

Experimental method

SOLUTION NMR