Structure formation during translocon-unassisted co-translational membrane protein folding

Abstract Correctly folded membrane proteins underlie a plethora of cellular processes, but little is known about how they fold. Knowledge of folding mechanisms centres on reversible folding of chemically denatured membrane proteins. However, this cannot replicate the unidirectional elongation of the...

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Autores principales:	Nicola J. Harris, Eamonn Reading, Kenichi Ataka, Lucjan Grzegorzewski, Kalypso Charalambous, Xia Liu, Ramona Schlesinger, Joachim Heberle, Paula J. Booth
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8f8480ca6af2428ea155c29546970aae
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spelling	oai:doaj.org-article:8f8480ca6af2428ea155c29546970aae2021-12-02T16:06:47ZStructure formation during translocon-unassisted co-translational membrane protein folding10.1038/s41598-017-08522-92045-2322https://doaj.org/article/8f8480ca6af2428ea155c29546970aae2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08522-9https://doaj.org/toc/2045-2322Abstract Correctly folded membrane proteins underlie a plethora of cellular processes, but little is known about how they fold. Knowledge of folding mechanisms centres on reversible folding of chemically denatured membrane proteins. However, this cannot replicate the unidirectional elongation of the protein chain during co-translational folding in the cell, where insertion is assisted by translocase apparatus. We show that a lipid membrane (devoid of translocase components) is sufficient for successful co-translational folding of two bacterial α-helical membrane proteins, DsbB and GlpG. Folding is spontaneous, thermodynamically driven, and the yield depends on lipid composition. Time-resolving structure formation during co-translational folding revealed different secondary and tertiary structure folding pathways for GlpG and DsbB that correlated with membrane interfacial and biological transmembrane amino acid hydrophobicity scales. Attempts to refold DsbB and GlpG from chemically denatured states into lipid membranes resulted in extensive aggregation. Co-translational insertion and folding is thus spontaneous and minimises aggregation whilst maximising correct folding.Nicola J. HarrisEamonn ReadingKenichi AtakaLucjan GrzegorzewskiKalypso CharalambousXia LiuRamona SchlesingerJoachim HeberlePaula J. BoothNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nicola J. Harris Eamonn Reading Kenichi Ataka Lucjan Grzegorzewski Kalypso Charalambous Xia Liu Ramona Schlesinger Joachim Heberle Paula J. Booth Structure formation during translocon-unassisted co-translational membrane protein folding
description	Abstract Correctly folded membrane proteins underlie a plethora of cellular processes, but little is known about how they fold. Knowledge of folding mechanisms centres on reversible folding of chemically denatured membrane proteins. However, this cannot replicate the unidirectional elongation of the protein chain during co-translational folding in the cell, where insertion is assisted by translocase apparatus. We show that a lipid membrane (devoid of translocase components) is sufficient for successful co-translational folding of two bacterial α-helical membrane proteins, DsbB and GlpG. Folding is spontaneous, thermodynamically driven, and the yield depends on lipid composition. Time-resolving structure formation during co-translational folding revealed different secondary and tertiary structure folding pathways for GlpG and DsbB that correlated with membrane interfacial and biological transmembrane amino acid hydrophobicity scales. Attempts to refold DsbB and GlpG from chemically denatured states into lipid membranes resulted in extensive aggregation. Co-translational insertion and folding is thus spontaneous and minimises aggregation whilst maximising correct folding.
format	article
author	Nicola J. Harris Eamonn Reading Kenichi Ataka Lucjan Grzegorzewski Kalypso Charalambous Xia Liu Ramona Schlesinger Joachim Heberle Paula J. Booth
author_facet	Nicola J. Harris Eamonn Reading Kenichi Ataka Lucjan Grzegorzewski Kalypso Charalambous Xia Liu Ramona Schlesinger Joachim Heberle Paula J. Booth
author_sort	Nicola J. Harris
title	Structure formation during translocon-unassisted co-translational membrane protein folding
title_short	Structure formation during translocon-unassisted co-translational membrane protein folding
title_full	Structure formation during translocon-unassisted co-translational membrane protein folding
title_fullStr	Structure formation during translocon-unassisted co-translational membrane protein folding
title_full_unstemmed	Structure formation during translocon-unassisted co-translational membrane protein folding
title_sort	structure formation during translocon-unassisted co-translational membrane protein folding
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/8f8480ca6af2428ea155c29546970aae
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Structure formation during translocon-unassisted co-translational membrane protein folding

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