The role of backbone hydrogen bonds in the transition state for protein folding of a PDZ domain.

Backbone hydrogen bonds are important for the structure and stability of proteins. However, since conventional site-directed mutagenesis cannot be applied to perturb the backbone, the contribution of these hydrogen bonds in protein folding and stability has been assessed only for a very limited set...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Søren W Pedersen, Greta Hultqvist, Kristian Strømgaard, Per Jemth
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/38b07bd6bbf847c7ac2c841f2629ba9a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:38b07bd6bbf847c7ac2c841f2629ba9a
record_format	dspace
spelling	oai:doaj.org-article:38b07bd6bbf847c7ac2c841f2629ba9a2021-11-18T08:22:23ZThe role of backbone hydrogen bonds in the transition state for protein folding of a PDZ domain.1932-620310.1371/journal.pone.0095619https://doaj.org/article/38b07bd6bbf847c7ac2c841f2629ba9a2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24748272/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Backbone hydrogen bonds are important for the structure and stability of proteins. However, since conventional site-directed mutagenesis cannot be applied to perturb the backbone, the contribution of these hydrogen bonds in protein folding and stability has been assessed only for a very limited set of small proteins. We have here investigated effects of five amide-to-ester mutations in the backbone of a PDZ domain, a 90-residue globular protein domain, to probe the influence of hydrogen bonds in a β-sheet for folding and stability. The amide-to-ester mutation removes NH-mediated hydrogen bonds and destabilizes hydrogen bonds formed by the carbonyl oxygen. The overall stability of the PDZ domain generally decreased for all amide-to-ester mutants due to an increase in the unfolding rate constant. For this particular region of the PDZ domain, it is therefore clear that native hydrogen bonds are formed after crossing of the rate-limiting barrier for folding. Moreover, three of the five amide-to-ester mutants displayed an increase in the folding rate constant suggesting that the hydrogen bonds are involved in non-native interactions in the transition state for folding.Søren W PedersenGreta HultqvistKristian StrømgaardPer JemthPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 4, p e95619 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Søren W Pedersen Greta Hultqvist Kristian Strømgaard Per Jemth The role of backbone hydrogen bonds in the transition state for protein folding of a PDZ domain.
description	Backbone hydrogen bonds are important for the structure and stability of proteins. However, since conventional site-directed mutagenesis cannot be applied to perturb the backbone, the contribution of these hydrogen bonds in protein folding and stability has been assessed only for a very limited set of small proteins. We have here investigated effects of five amide-to-ester mutations in the backbone of a PDZ domain, a 90-residue globular protein domain, to probe the influence of hydrogen bonds in a β-sheet for folding and stability. The amide-to-ester mutation removes NH-mediated hydrogen bonds and destabilizes hydrogen bonds formed by the carbonyl oxygen. The overall stability of the PDZ domain generally decreased for all amide-to-ester mutants due to an increase in the unfolding rate constant. For this particular region of the PDZ domain, it is therefore clear that native hydrogen bonds are formed after crossing of the rate-limiting barrier for folding. Moreover, three of the five amide-to-ester mutants displayed an increase in the folding rate constant suggesting that the hydrogen bonds are involved in non-native interactions in the transition state for folding.
format	article
author	Søren W Pedersen Greta Hultqvist Kristian Strømgaard Per Jemth
author_facet	Søren W Pedersen Greta Hultqvist Kristian Strømgaard Per Jemth
author_sort	Søren W Pedersen
title	The role of backbone hydrogen bonds in the transition state for protein folding of a PDZ domain.
title_short	The role of backbone hydrogen bonds in the transition state for protein folding of a PDZ domain.
title_full	The role of backbone hydrogen bonds in the transition state for protein folding of a PDZ domain.
title_fullStr	The role of backbone hydrogen bonds in the transition state for protein folding of a PDZ domain.
title_full_unstemmed	The role of backbone hydrogen bonds in the transition state for protein folding of a PDZ domain.
title_sort	role of backbone hydrogen bonds in the transition state for protein folding of a pdz domain.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/38b07bd6bbf847c7ac2c841f2629ba9a
work_keys_str_mv	AT sørenwpedersen theroleofbackbonehydrogenbondsinthetransitionstateforproteinfoldingofapdzdomain AT gretahultqvist theroleofbackbonehydrogenbondsinthetransitionstateforproteinfoldingofapdzdomain AT kristianstrømgaard theroleofbackbonehydrogenbondsinthetransitionstateforproteinfoldingofapdzdomain AT perjemth theroleofbackbonehydrogenbondsinthetransitionstateforproteinfoldingofapdzdomain AT sørenwpedersen roleofbackbonehydrogenbondsinthetransitionstateforproteinfoldingofapdzdomain AT gretahultqvist roleofbackbonehydrogenbondsinthetransitionstateforproteinfoldingofapdzdomain AT kristianstrømgaard roleofbackbonehydrogenbondsinthetransitionstateforproteinfoldingofapdzdomain AT perjemth roleofbackbonehydrogenbondsinthetransitionstateforproteinfoldingofapdzdomain
_version_	1718421853376086016

The role of backbone hydrogen bonds in the transition state for protein folding of a PDZ domain.

Ejemplares similares