Cargando…

β-Barrels and Amyloids: Structural Transitions, Biological Functions, and Pathogenesis

Insoluble protein aggregates with fibrillar morphology called amyloids and β-barrel proteins both share a β-sheet-rich structure. Correctly folded β-barrel proteins can not only function in monomeric (dimeric) form, but also tend to interact with one another—followed, in several cases, by formation...

Descripción completa

Detalles Bibliográficos
Autores principales: Sulatskaya, Anna I., Kosolapova, Anastasiia O., Bobylev, Alexander G., Belousov, Mikhail V., Antonets, Kirill S., Sulatsky, Maksim I., Kuznetsova, Irina M., Turoverov, Konstantin K., Stepanenko, Olesya V., Nizhnikov, Anton A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582884/
https://www.ncbi.nlm.nih.gov/pubmed/34768745
http://dx.doi.org/10.3390/ijms222111316
_version_ 1784597088546324480
author Sulatskaya, Anna I.
Kosolapova, Anastasiia O.
Bobylev, Alexander G.
Belousov, Mikhail V.
Antonets, Kirill S.
Sulatsky, Maksim I.
Kuznetsova, Irina M.
Turoverov, Konstantin K.
Stepanenko, Olesya V.
Nizhnikov, Anton A.
author_facet Sulatskaya, Anna I.
Kosolapova, Anastasiia O.
Bobylev, Alexander G.
Belousov, Mikhail V.
Antonets, Kirill S.
Sulatsky, Maksim I.
Kuznetsova, Irina M.
Turoverov, Konstantin K.
Stepanenko, Olesya V.
Nizhnikov, Anton A.
author_sort Sulatskaya, Anna I.
collection PubMed
description Insoluble protein aggregates with fibrillar morphology called amyloids and β-barrel proteins both share a β-sheet-rich structure. Correctly folded β-barrel proteins can not only function in monomeric (dimeric) form, but also tend to interact with one another—followed, in several cases, by formation of higher order oligomers or even aggregates. In recent years, findings proving that β-barrel proteins can adopt cross-β amyloid folds have emerged. Different β-barrel proteins were shown to form amyloid fibrils in vitro. The formation of functional amyloids in vivo by β-barrel proteins for which the amyloid state is native was also discovered. In particular, several prokaryotic and eukaryotic proteins with β-barrel domains were demonstrated to form amyloids in vivo, where they participate in interspecies interactions and nutrient storage, respectively. According to recent observations, despite the variety of primary structures of amyloid-forming proteins, most of them can adopt a conformational state with the β-barrel topology. This state can be intermediate on the pathway of fibrillogenesis (“on-pathway state”), or can be formed as a result of an alternative assembly of partially unfolded monomers (“off-pathway state”). The β-barrel oligomers formed by amyloid proteins possess toxicity, and are likely to be involved in the development of amyloidoses, thus representing promising targets for potential therapy of these incurable diseases. Considering rapidly growing discoveries of the amyloid-forming β-barrels, we may suggest that their real number and diversity of functions are significantly higher than identified to date, and represent only “the tip of the iceberg”. Here, we summarize the data on the amyloid-forming β-barrel proteins, their physicochemical properties, and their biological functions, and discuss probable means and consequences of the amyloidogenesis of these proteins, along with structural relationships between these two widespread types of β-folds.
format Online
Article
Text
id pubmed-8582884
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-85828842021-11-12 β-Barrels and Amyloids: Structural Transitions, Biological Functions, and Pathogenesis Sulatskaya, Anna I. Kosolapova, Anastasiia O. Bobylev, Alexander G. Belousov, Mikhail V. Antonets, Kirill S. Sulatsky, Maksim I. Kuznetsova, Irina M. Turoverov, Konstantin K. Stepanenko, Olesya V. Nizhnikov, Anton A. Int J Mol Sci Review Insoluble protein aggregates with fibrillar morphology called amyloids and β-barrel proteins both share a β-sheet-rich structure. Correctly folded β-barrel proteins can not only function in monomeric (dimeric) form, but also tend to interact with one another—followed, in several cases, by formation of higher order oligomers or even aggregates. In recent years, findings proving that β-barrel proteins can adopt cross-β amyloid folds have emerged. Different β-barrel proteins were shown to form amyloid fibrils in vitro. The formation of functional amyloids in vivo by β-barrel proteins for which the amyloid state is native was also discovered. In particular, several prokaryotic and eukaryotic proteins with β-barrel domains were demonstrated to form amyloids in vivo, where they participate in interspecies interactions and nutrient storage, respectively. According to recent observations, despite the variety of primary structures of amyloid-forming proteins, most of them can adopt a conformational state with the β-barrel topology. This state can be intermediate on the pathway of fibrillogenesis (“on-pathway state”), or can be formed as a result of an alternative assembly of partially unfolded monomers (“off-pathway state”). The β-barrel oligomers formed by amyloid proteins possess toxicity, and are likely to be involved in the development of amyloidoses, thus representing promising targets for potential therapy of these incurable diseases. Considering rapidly growing discoveries of the amyloid-forming β-barrels, we may suggest that their real number and diversity of functions are significantly higher than identified to date, and represent only “the tip of the iceberg”. Here, we summarize the data on the amyloid-forming β-barrel proteins, their physicochemical properties, and their biological functions, and discuss probable means and consequences of the amyloidogenesis of these proteins, along with structural relationships between these two widespread types of β-folds. MDPI 2021-10-20 /pmc/articles/PMC8582884/ /pubmed/34768745 http://dx.doi.org/10.3390/ijms222111316 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Sulatskaya, Anna I.
Kosolapova, Anastasiia O.
Bobylev, Alexander G.
Belousov, Mikhail V.
Antonets, Kirill S.
Sulatsky, Maksim I.
Kuznetsova, Irina M.
Turoverov, Konstantin K.
Stepanenko, Olesya V.
Nizhnikov, Anton A.
β-Barrels and Amyloids: Structural Transitions, Biological Functions, and Pathogenesis
title β-Barrels and Amyloids: Structural Transitions, Biological Functions, and Pathogenesis
title_full β-Barrels and Amyloids: Structural Transitions, Biological Functions, and Pathogenesis
title_fullStr β-Barrels and Amyloids: Structural Transitions, Biological Functions, and Pathogenesis
title_full_unstemmed β-Barrels and Amyloids: Structural Transitions, Biological Functions, and Pathogenesis
title_short β-Barrels and Amyloids: Structural Transitions, Biological Functions, and Pathogenesis
title_sort β-barrels and amyloids: structural transitions, biological functions, and pathogenesis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582884/
https://www.ncbi.nlm.nih.gov/pubmed/34768745
http://dx.doi.org/10.3390/ijms222111316
work_keys_str_mv AT sulatskayaannai bbarrelsandamyloidsstructuraltransitionsbiologicalfunctionsandpathogenesis
AT kosolapovaanastasiiao bbarrelsandamyloidsstructuraltransitionsbiologicalfunctionsandpathogenesis
AT bobylevalexanderg bbarrelsandamyloidsstructuraltransitionsbiologicalfunctionsandpathogenesis
AT belousovmikhailv bbarrelsandamyloidsstructuraltransitionsbiologicalfunctionsandpathogenesis
AT antonetskirills bbarrelsandamyloidsstructuraltransitionsbiologicalfunctionsandpathogenesis
AT sulatskymaksimi bbarrelsandamyloidsstructuraltransitionsbiologicalfunctionsandpathogenesis
AT kuznetsovairinam bbarrelsandamyloidsstructuraltransitionsbiologicalfunctionsandpathogenesis
AT turoverovkonstantink bbarrelsandamyloidsstructuraltransitionsbiologicalfunctionsandpathogenesis
AT stepanenkoolesyav bbarrelsandamyloidsstructuraltransitionsbiologicalfunctionsandpathogenesis
AT nizhnikovantona bbarrelsandamyloidsstructuraltransitionsbiologicalfunctionsandpathogenesis