Conformational exchange divergence along the evolutionary pathway of eosinophil-associated ribonucleases.

Autor:	Bernard DN; Centre Armand-Frappier Santé Biotechnologie, Institut national de la recherche scientifique (INRS), Université du Québec, 531 Boulevard des Prairies, Laval, QC H7V 1B7, Canada., Narayanan C; Centre Armand-Frappier Santé Biotechnologie, Institut national de la recherche scientifique (INRS), Université du Québec, 531 Boulevard des Prairies, Laval, QC H7V 1B7, Canada; Department of Chemistry, New Jersey City University, Jersey City, NJ 07305, USA., Hempel T; Department of Mathematics and Computer Science, Freie Universität Berlin, Arnimallee 12, 14195 Berlin, Germany; Department of Physics, Freie Universität Berlin, Arnimallee 14, 14195 Berlin, Germany., Bafna K; Department of Biochemistry & Cellular and Molecular Biology, University of Tennessee, Knoxville, TN 37996, USA., Bhojane PP; Department of Biochemistry & Cellular and Molecular Biology, University of Tennessee, Knoxville, TN 37996, USA., Létourneau M; Centre Armand-Frappier Santé Biotechnologie, Institut national de la recherche scientifique (INRS), Université du Québec, 531 Boulevard des Prairies, Laval, QC H7V 1B7, Canada., Howell EE; Department of Biochemistry & Cellular and Molecular Biology, University of Tennessee, Knoxville, TN 37996, USA., Agarwal PK; Department of Physiological Sciences and High-Performance Computing Center, Oklahoma State University, Stillwater, OK 74078, USA. Electronic address: pratul.agarwal@okstate.edu., Doucet N; Centre Armand-Frappier Santé Biotechnologie, Institut national de la recherche scientifique (INRS), Université du Québec, 531 Boulevard des Prairies, Laval, QC H7V 1B7, Canada; PROTEO, the Québec Network for Research on Protein Function, Engineering, and Applications, Université Laval, 1045 Avenue de la Médecine, Québec, QC G1V 0A6, Canada. Electronic address: nicolas.doucet@inrs.ca.
Jazyk:	angličtina
Zdroj:	Structure (London, England : 1993) [Structure] 2023 Mar 02; Vol. 31 (3), pp. 329-342.e4. Date of Electronic Publication: 2023 Jan 16.
DOI:	10.1016/j.str.2022.12.011
Abstrakt:	The evolutionary role of conformational exchange in the emergence and preservation of function within structural homologs remains elusive. While protein engineering has revealed the importance of flexibility in function, productive modulation of atomic-scale dynamics has only been achieved on a finite number of distinct folds. Allosteric control of unique members within dynamically diverse structural families requires a better appreciation of exchange phenomena. Here, we examined the functional and structural role of conformational exchange within eosinophil-associated ribonucleases. Biological and catalytic activity of various EARs was performed in parallel to mapping their conformational behavior on multiple timescales using NMR and computational analyses. Despite functional conservation and conformational seclusion to a specific domain, we show that EARs can display similar or distinct motional profiles, implying divergence rather than conservation of flexibility. Comparing progressively more distant enzymes should unravel how this subfamily has evolved new functions and/or altered their behavior at the molecular level. Competing Interests: Declaration of interests Pratul K. Agarwal is the founder of the company Arium BioLabs, LLC. (Copyright © 2022 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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