Title
Design and characterization of a protein fold switching network
Author
Biao Ruan, Yanan He, Yingwei Chen, Eun Jung Choi, Yihong Chen, Dana Motabar, Tsega Solomon, Richard Simmerman, Thomas Kauffman, D. Travis Gallagher, John Orban & Philip N. Bryan
Year
2023
Journal
Nature Communications
Abstract
To better understand how amino acid sequence encodes protein structure, we engineered mutational pathways that connect three common folds (3α, β−grasp, and α/β−plait). The structures of proteins at high sequence-identity intersections in the pathways (nodes) were determined using NMR spectroscopy and analyzed for stability and function. To generate nodes, the amino acid sequence encoding a smaller fold is embedded in the structure of an ~50% larger fold and a new sequence compatible with two sets of native interactions is designed. This generates protein pairs with a 3α or β−grasp fold in the smaller form but an α/β−plait fold in the larger form. Further, embedding smaller antagonistic folds creates critical states in the larger folds such that single amino acid substitutions can switch both their fold and function. The results help explain the underlying ambiguity in the protein folding code and show that new protein structures can evolve via abrupt fold switching.
Full Article
Instrument
J-1100
Keywords
amino acid, protein structure,