Artificial DnaJ Protein for protein production and conformational diseases

Abstract For secreted proteins, proper protein folding is essential not only for biological function but also for secretion itself. Proteins with folding problems are trapped in the endoplasmic reticulum (ER) and are eventually degraded in the cytoplasm. In this study, we exploited co-expression of...

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Autores principales:	Akinori Hishiya, Keizo Koya
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8bbc8d7634574565816e06db2aa92957
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spelling	oai:doaj.org-article:8bbc8d7634574565816e06db2aa929572021-12-02T15:05:43ZArtificial DnaJ Protein for protein production and conformational diseases10.1038/s41598-017-09067-72045-2322https://doaj.org/article/8bbc8d7634574565816e06db2aa929572017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09067-7https://doaj.org/toc/2045-2322Abstract For secreted proteins, proper protein folding is essential not only for biological function but also for secretion itself. Proteins with folding problems are trapped in the endoplasmic reticulum (ER) and are eventually degraded in the cytoplasm. In this study, we exploited co-expression of an artificial fusion protein, based on the sequence of a DnaJ protein, which could interact as co-chaperones in the Hsp70-based protein-folding system, with target recombinant secreted proteins to enhance their production and secretion. The J-domain sequence or a fragment thereof was conjugated to a target protein–binding domain that was capable of binding to a portion of the target-protein sequence. Production of many of the target proteins was significantly upregulated when co-expressed with the J-domain fusion protein. Surprisingly, the enhancement of secretion was observed even when the J-domain had a mutation in the HPD motif, which is necessary for J-protein–Hsp70 interactions, suggesting the phenomenon observed is independent on functional J-protein–Hsp70 interactions. This technology has great potential for not only enhancing the production of recombinant proteins, but also to treat conformational diseases such as cystic fibrosis, and Alpha-1 antitrypsin deficiency.Akinori HishiyaKeizo KoyaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Akinori Hishiya Keizo Koya Artificial DnaJ Protein for protein production and conformational diseases
description	Abstract For secreted proteins, proper protein folding is essential not only for biological function but also for secretion itself. Proteins with folding problems are trapped in the endoplasmic reticulum (ER) and are eventually degraded in the cytoplasm. In this study, we exploited co-expression of an artificial fusion protein, based on the sequence of a DnaJ protein, which could interact as co-chaperones in the Hsp70-based protein-folding system, with target recombinant secreted proteins to enhance their production and secretion. The J-domain sequence or a fragment thereof was conjugated to a target protein–binding domain that was capable of binding to a portion of the target-protein sequence. Production of many of the target proteins was significantly upregulated when co-expressed with the J-domain fusion protein. Surprisingly, the enhancement of secretion was observed even when the J-domain had a mutation in the HPD motif, which is necessary for J-protein–Hsp70 interactions, suggesting the phenomenon observed is independent on functional J-protein–Hsp70 interactions. This technology has great potential for not only enhancing the production of recombinant proteins, but also to treat conformational diseases such as cystic fibrosis, and Alpha-1 antitrypsin deficiency.
format	article
author	Akinori Hishiya Keizo Koya
author_facet	Akinori Hishiya Keizo Koya
author_sort	Akinori Hishiya
title	Artificial DnaJ Protein for protein production and conformational diseases
title_short	Artificial DnaJ Protein for protein production and conformational diseases
title_full	Artificial DnaJ Protein for protein production and conformational diseases
title_fullStr	Artificial DnaJ Protein for protein production and conformational diseases
title_full_unstemmed	Artificial DnaJ Protein for protein production and conformational diseases
title_sort	artificial dnaj protein for protein production and conformational diseases
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/8bbc8d7634574565816e06db2aa92957
work_keys_str_mv	AT akinorihishiya artificialdnajproteinforproteinproductionandconformationaldiseases AT keizokoya artificialdnajproteinforproteinproductionandconformationaldiseases
_version_	1718388716607635456

Artificial DnaJ Protein for protein production and conformational diseases

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