Skip to main content
U.S. flag

An official website of the United States government

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

Design and characterization of a protein fold switching network

Published

Author(s)

David Travis Gallagher, Biao Ruan, Yanan He, Yingwei Chen, Eun Jung Choi, Yihong Chen, Dana Motabar, Tsega Solomon, Richard Simmerman, Thomas Kauffman, John Orban, Philip Bryan

Abstract

Protein sequences encoding three common small folds (3-alpha, beta-grasp, and alpha/beta plait) were connected in a network of mutational pathways that intersect at high-identity sequences, termed nodes. The structures of proteins around nodes were determined using NMR spectroscopy and analyzed for stability and binding function. To generate nodes, the amino acid sequence encoding a shorter fold (3-alpha or beta-grasp) is embedded in the structure of the 50% longer alpha/beta plait fold and a new sequence is designed that satisfies two sets of native interactions. This leads to protein pairs with a 3-alpha or beta-grasp fold in the shorter form but an alpha-beta plait fold in the longer form. Further, embedding smaller antagonistic folds in longer folds creates critical states in the longer folds such that single amino acid substitutions can switch both their fold and function. This suggests that abrupt fold switching may be a mechanism of evolving new protein structures and functions
Citation
Nature Communications
Volume
14

Keywords

protein fold switching, metamorphic, design, NMR structure, evolution

Citation

Gallagher, D. , Ruan, B. , He, Y. , Chen, Y. , Choi, E. , Chen, Y. , Motabar, D. , Solomon, T. , Simmerman, R. , Kauffman, T. , Orban, J. and Bryan, P. (2023), Design and characterization of a protein fold switching network, Nature Communications, [online], https://doi.org/10.1038/s41467-023-36065-3 (Accessed July 13, 2024)

Issues

If you have any questions about this publication or are having problems accessing it, please contact reflib@nist.gov.

Created January 26, 2023, Updated August 29, 2023