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Recombinant Bri3 BRICHOS domain is a molecular chaperone with effect against amyloid formation and non-fibrillar protein aggregation

Molecular chaperones assist proteins in achieving a functional structure and prevent them from misfolding into aggregates, including disease-associated deposits. The BRICHOS domain from familial dementia associated protein Bri2 (or ITM2B) probably chaperones its specific proprotein region with high...

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Autores principales: Poska, Helen, Leppert, Axel, Tigro, Helene, Zhong, Xueying, Kaldmäe, Margit, Nilsson, Harriet E, Hebert, Hans, Chen, Gefei, Johansson, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299998/
https://www.ncbi.nlm.nih.gov/pubmed/32555390
http://dx.doi.org/10.1038/s41598-020-66718-y
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author Poska, Helen
Leppert, Axel
Tigro, Helene
Zhong, Xueying
Kaldmäe, Margit
Nilsson, Harriet E
Hebert, Hans
Chen, Gefei
Johansson, Jan
author_facet Poska, Helen
Leppert, Axel
Tigro, Helene
Zhong, Xueying
Kaldmäe, Margit
Nilsson, Harriet E
Hebert, Hans
Chen, Gefei
Johansson, Jan
author_sort Poska, Helen
collection PubMed
description Molecular chaperones assist proteins in achieving a functional structure and prevent them from misfolding into aggregates, including disease-associated deposits. The BRICHOS domain from familial dementia associated protein Bri2 (or ITM2B) probably chaperones its specific proprotein region with high β-sheet propensity during biosynthesis. Recently, Bri2 BRICHOS activity was found to extend to other amyloidogenic, fibril forming peptides, in particular, Alzheimer’s disease associated amyloid-β peptide, as well as to amorphous aggregate forming proteins. However, the biological functions of the central nervous system specific homologue Bri3 BRICHOS are still to be elucidated. Here we give a detailed characterisation of the recombinant human (rh) Bri3 BRICHOS domain and compare its structural and functional properties with rh Bri2 BRICHOS. The results show that rh Bri3 BRICHOS forms more and larger oligomers, somewhat more efficiently prevents non-fibrillar protein aggregation, and less efficiently reduces Aβ42 fibril formation compared to rh Bri2 BRICHOS. This suggests that Bri2 and Bri3 BRICHOS have overlapping molecular mechanisms and that their apparently different tissue expression and processing may result in different physiological functions.
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spelling pubmed-72999982020-06-18 Recombinant Bri3 BRICHOS domain is a molecular chaperone with effect against amyloid formation and non-fibrillar protein aggregation Poska, Helen Leppert, Axel Tigro, Helene Zhong, Xueying Kaldmäe, Margit Nilsson, Harriet E Hebert, Hans Chen, Gefei Johansson, Jan Sci Rep Article Molecular chaperones assist proteins in achieving a functional structure and prevent them from misfolding into aggregates, including disease-associated deposits. The BRICHOS domain from familial dementia associated protein Bri2 (or ITM2B) probably chaperones its specific proprotein region with high β-sheet propensity during biosynthesis. Recently, Bri2 BRICHOS activity was found to extend to other amyloidogenic, fibril forming peptides, in particular, Alzheimer’s disease associated amyloid-β peptide, as well as to amorphous aggregate forming proteins. However, the biological functions of the central nervous system specific homologue Bri3 BRICHOS are still to be elucidated. Here we give a detailed characterisation of the recombinant human (rh) Bri3 BRICHOS domain and compare its structural and functional properties with rh Bri2 BRICHOS. The results show that rh Bri3 BRICHOS forms more and larger oligomers, somewhat more efficiently prevents non-fibrillar protein aggregation, and less efficiently reduces Aβ42 fibril formation compared to rh Bri2 BRICHOS. This suggests that Bri2 and Bri3 BRICHOS have overlapping molecular mechanisms and that their apparently different tissue expression and processing may result in different physiological functions. Nature Publishing Group UK 2020-06-17 /pmc/articles/PMC7299998/ /pubmed/32555390 http://dx.doi.org/10.1038/s41598-020-66718-y Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Poska, Helen
Leppert, Axel
Tigro, Helene
Zhong, Xueying
Kaldmäe, Margit
Nilsson, Harriet E
Hebert, Hans
Chen, Gefei
Johansson, Jan
Recombinant Bri3 BRICHOS domain is a molecular chaperone with effect against amyloid formation and non-fibrillar protein aggregation
title Recombinant Bri3 BRICHOS domain is a molecular chaperone with effect against amyloid formation and non-fibrillar protein aggregation
title_full Recombinant Bri3 BRICHOS domain is a molecular chaperone with effect against amyloid formation and non-fibrillar protein aggregation
title_fullStr Recombinant Bri3 BRICHOS domain is a molecular chaperone with effect against amyloid formation and non-fibrillar protein aggregation
title_full_unstemmed Recombinant Bri3 BRICHOS domain is a molecular chaperone with effect against amyloid formation and non-fibrillar protein aggregation
title_short Recombinant Bri3 BRICHOS domain is a molecular chaperone with effect against amyloid formation and non-fibrillar protein aggregation
title_sort recombinant bri3 brichos domain is a molecular chaperone with effect against amyloid formation and non-fibrillar protein aggregation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299998/
https://www.ncbi.nlm.nih.gov/pubmed/32555390
http://dx.doi.org/10.1038/s41598-020-66718-y
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