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Co-Translational Folding of Multi-Domain Proteins

The majority of proteins in nature are composed of multiple domains connected in a single polypeptide. How these long sequences fold into functional structures without forming toxic misfolds or aggregates is poorly understood. Their folding is inextricably linked to protein synthesis and interaction...

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Detalles Bibliográficos
Autores principales: Rajasekaran, Nandakumar, Kaiser, Christian M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9065291/
https://www.ncbi.nlm.nih.gov/pubmed/35517860
http://dx.doi.org/10.3389/fmolb.2022.869027
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author Rajasekaran, Nandakumar
Kaiser, Christian M.
author_facet Rajasekaran, Nandakumar
Kaiser, Christian M.
author_sort Rajasekaran, Nandakumar
collection PubMed
description The majority of proteins in nature are composed of multiple domains connected in a single polypeptide. How these long sequences fold into functional structures without forming toxic misfolds or aggregates is poorly understood. Their folding is inextricably linked to protein synthesis and interactions with cellular machinery, making mechanistic studies challenging. Recent progress has revealed critical features of multi-domain protein folding in isolation and in the context of translation by the ribosome. In this review, we discuss challenges and progress in understanding multi-domain protein folding, and highlight how molecular interactions shape folding and misfolding pathways. With the development of new approaches and model systems, the stage is now set for mechanistically exploring the folding of large multi-domain proteins.
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spelling pubmed-90652912022-05-04 Co-Translational Folding of Multi-Domain Proteins Rajasekaran, Nandakumar Kaiser, Christian M. Front Mol Biosci Molecular Biosciences The majority of proteins in nature are composed of multiple domains connected in a single polypeptide. How these long sequences fold into functional structures without forming toxic misfolds or aggregates is poorly understood. Their folding is inextricably linked to protein synthesis and interactions with cellular machinery, making mechanistic studies challenging. Recent progress has revealed critical features of multi-domain protein folding in isolation and in the context of translation by the ribosome. In this review, we discuss challenges and progress in understanding multi-domain protein folding, and highlight how molecular interactions shape folding and misfolding pathways. With the development of new approaches and model systems, the stage is now set for mechanistically exploring the folding of large multi-domain proteins. Frontiers Media S.A. 2022-04-20 /pmc/articles/PMC9065291/ /pubmed/35517860 http://dx.doi.org/10.3389/fmolb.2022.869027 Text en Copyright © 2022 Rajasekaran and Kaiser. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Rajasekaran, Nandakumar
Kaiser, Christian M.
Co-Translational Folding of Multi-Domain Proteins
title Co-Translational Folding of Multi-Domain Proteins
title_full Co-Translational Folding of Multi-Domain Proteins
title_fullStr Co-Translational Folding of Multi-Domain Proteins
title_full_unstemmed Co-Translational Folding of Multi-Domain Proteins
title_short Co-Translational Folding of Multi-Domain Proteins
title_sort co-translational folding of multi-domain proteins
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9065291/
https://www.ncbi.nlm.nih.gov/pubmed/35517860
http://dx.doi.org/10.3389/fmolb.2022.869027
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