Residue coevolution and mutational landscape for OmpR and NarL response regulator subfamilies.
Autor: | Shibata M; Graduate School of Humanities and Sciences, Ochanomizu University, Bunkyo, Tokyo, Japan; Center for Theoretical Biological Physics, Rice University, Houston Texas., Lin X; Department of Physics, North Carolina State University, Raleigh, North Carolina; Bioinformatics Research Center, North Carolina State University, Raleigh, North Carolina., Onuchic JN; Center for Theoretical Biological Physics, Rice University, Houston Texas; Department of Physics and Astronomy, Chemistry, and Biosciences, Rice University, Houston, Texas., Yura K; Graduate School of Humanities and Sciences, Ochanomizu University, Bunkyo, Tokyo, Japan; Center for Interdisciplinary AI and Data Science, Ochanomizu University, Bunkyo, Tokyo, Japan; Graduate School of Advanced Science and Engineering, Waseda University, Shinjuku, Tokyo, Japan., Cheng RR; Department of Chemistry, University of Kentucky, Lexington, Kentucky. Electronic address: ryan.r.cheng@uky.edu. |
---|---|
Jazyk: | angličtina |
Zdroj: | Biophysical journal [Biophys J] 2024 Mar 19; Vol. 123 (6), pp. 681-692. Date of Electronic Publication: 2024 Jan 30. |
DOI: | 10.1016/j.bpj.2024.01.028 |
Abstrakt: | DNA-binding response regulators (DBRRs) are a broad class of proteins that operate in tandem with their partner kinase proteins to form two-component signal transduction systems in bacteria. Typical DBRRs are composed of two domains where the conserved N-terminal domain accepts transduced signals and the evolutionarily diverse C-terminal domain binds to DNA. These domains are assumed to be functionally independent, and hence recombination of the two domains should yield novel DBRRs of arbitrary input/output response, which can be used as biosensors. This idea has been proved to be successful in some cases; yet, the error rate is not trivial. Improvement of the success rate of this technique requires a deeper understanding of the linker-domain and inter-domain residue interactions, which have not yet been thoroughly examined. Here, we studied residue coevolution of DBRRs of the two main subfamilies (OmpR and NarL) using large collections of bacterial amino acid sequences to extensively investigate the evolutionary signatures of linker-domain and inter-domain residue interactions. Coevolutionary analysis uncovered evolutionarily selected linker-domain and inter-domain residue interactions of known experimental structures, as well as previously unknown inter-domain residue interactions. We examined the possibility of these inter-domain residue interactions as contacts that stabilize an inactive conformation of the DBRR where DNA binding is inhibited for both subfamilies. The newly gained insights on linker-domain/inter-domain residue interactions and shared inactivation mechanisms improve the understanding of the functional mechanism of DBRRs, providing clues to efficiently create functional DBRR-based biosensors. Additionally, we show the feasibility of applying coevolutionary landscape models to predict the functionality of domain-swapped DBRR proteins. The presented result demonstrates that sequence information can be used to filter out bioengineered DBRR proteins that are predicted to be nonfunctional due to a high negative predictive value. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 Biophysical Society. Published by Elsevier Inc. All rights reserved.) |
Databáze: | MEDLINE |
Externí odkaz: |