Ancestral sequence reconstruction dissects structural and functional differences among eosinophil ribonucleases
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved..
Evolutionarily conserved structural folds can give rise to diverse biological functions, yet predicting atomic-scale interactions that contribute to the emergence of novel activities within such folds remains challenging. Pancreatic-type ribonucleases illustrate this complexity, sharing a core structure that has evolved to accommodate varied functions. In this study, we used ancestral sequence reconstruction to probe evolutionary and molecular determinants that distinguish biological activities within eosinophil members of the RNase 2/3 subfamily. Our investigation unveils functional, structural, and dynamical behaviors that differentiate the evolved ancestor AncRNase from its contemporary eosinophil RNase orthologs. Leveraging the potential of ancestral reconstruction for protein engineering, we used AncRNase predictions to design a minimal 4-residue variant that transforms human RNase 2 into a chimeric enzyme endowed with the antimicrobial and cytotoxic activities of RNase 3 members. This work provides unique insights into mutational and evolutionary pathways governing structure, function, and conformational states within the eosinophil RNase subfamily, offering potential for targeted modulation of RNase-associated functions.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
The Journal of biological chemistry - (2024) vom: 06. Apr., Seite 107280 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tran, Thi Thanh Quynh [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Revised 08.04.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1016/j.jbc.2024.107280 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370781570 |
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| 245 | 1 | 0 | |a Ancestral sequence reconstruction dissects structural and functional differences among eosinophil ribonucleases |
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| 520 | |a Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Evolutionarily conserved structural folds can give rise to diverse biological functions, yet predicting atomic-scale interactions that contribute to the emergence of novel activities within such folds remains challenging. Pancreatic-type ribonucleases illustrate this complexity, sharing a core structure that has evolved to accommodate varied functions. In this study, we used ancestral sequence reconstruction to probe evolutionary and molecular determinants that distinguish biological activities within eosinophil members of the RNase 2/3 subfamily. Our investigation unveils functional, structural, and dynamical behaviors that differentiate the evolved ancestor AncRNase from its contemporary eosinophil RNase orthologs. Leveraging the potential of ancestral reconstruction for protein engineering, we used AncRNase predictions to design a minimal 4-residue variant that transforms human RNase 2 into a chimeric enzyme endowed with the antimicrobial and cytotoxic activities of RNase 3 members. This work provides unique insights into mutational and evolutionary pathways governing structure, function, and conformational states within the eosinophil RNase subfamily, offering potential for targeted modulation of RNase-associated functions | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a RNase 2 | |
| 650 | 4 | |a RNase 3 | |
| 650 | 4 | |a X-ray crystallography | |
| 650 | 4 | |a ancestral RNase | |
| 650 | 4 | |a ancestral sequence reconstruction | |
| 650 | 4 | |a chimeragenesis | |
| 650 | 4 | |a eosinophil | |
| 650 | 4 | |a eosinophil cationic protein | |
| 650 | 4 | |a eosinophil-derived neurotoxin | |
| 650 | 4 | |a molecular dynamics | |
| 650 | 4 | |a protein evolution | |
| 650 | 4 | |a structural biology | |
| 700 | 1 | |a Narayanan, Chitra |e verfasserin |4 aut | |
| 700 | 1 | |a Loes, Andrea N |e verfasserin |4 aut | |
| 700 | 1 | |a Click, Timothy H |e verfasserin |4 aut | |
| 700 | 1 | |a Pham, N T Hang |e verfasserin |4 aut | |
| 700 | 1 | |a Létourneau, Myriam |e verfasserin |4 aut | |
| 700 | 1 | |a Harms, Michael J |e verfasserin |4 aut | |
| 700 | 1 | |a Calmettes, Charles |e verfasserin |4 aut | |
| 700 | 1 | |a Agarwal, Pratul K |e verfasserin |4 aut | |
| 700 | 1 | |a Doucet, Nicolas |e verfasserin |4 aut | |
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