Conformational analysis of isolated domains of Helicobacter pylori CagA.

The CagA protein of Helicobacter pylori is associated with increased virulence and gastric cancer risk. CagA is translocated into the host cell by a H. pylori type IV secretion system via mechanisms that are poorly understood. Translocated CagA interacts with numerous host factors, altering a variet...

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Autores principales:	Amanda P Woon, Abolghasem Tohidpour, Hernan Alonso, Yumiko Saijo-Hamano, Terry Kwok, Anna Roujeinikova
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9f14f6a09eed49eb84c834b795590d73
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spelling	oai:doaj.org-article:9f14f6a09eed49eb84c834b795590d732021-11-18T08:48:41ZConformational analysis of isolated domains of Helicobacter pylori CagA.1932-620310.1371/journal.pone.0079367https://doaj.org/article/9f14f6a09eed49eb84c834b795590d732013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24223932/?tool=EBIhttps://doaj.org/toc/1932-6203The CagA protein of Helicobacter pylori is associated with increased virulence and gastric cancer risk. CagA is translocated into the host cell by a H. pylori type IV secretion system via mechanisms that are poorly understood. Translocated CagA interacts with numerous host factors, altering a variety of host signalling pathways. The recently determined crystal structure of C-terminally-truncated CagA indicated the presence of two domains: the smaller, flexible N-terminal domain and the larger, middle domain. In this study, we have investigated the conformation, oligomeric state and stability of the N-terminal, middle and glutamate-proline-isoleucine-tyrosine-alanine (EPIYA)-repeats domains. All three domains are monomeric, suggesting that the multimerisation of CagA observed in infected cells is likely to be mediated not by CagA itself but by its interacting partners. The middle and the C-terminal domains, but not the N-terminal domain, are capable of refolding spontaneously upon heat denaturation, lending support to the hypothesis that unfolded CagA is threaded C-terminus first through the type IV secretion channel with its N-terminal domain, which likely requires interactions with other domains to refold, being threaded last. Our findings also revealed that the C-terminal EPIYA-repeats domain of CagA exists in an intrinsically disordered premolten globule state with regions in PPII conformation--a feature that is shared by many scaffold proteins that bind multiple protein components of signalling pathways. Taken together, these results provide a deeper understanding of the physicochemical properties of CagA that underpin its complex cellular and oncogenic functions.Amanda P WoonAbolghasem TohidpourHernan AlonsoYumiko Saijo-HamanoTerry KwokAnna RoujeinikovaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e79367 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Amanda P Woon Abolghasem Tohidpour Hernan Alonso Yumiko Saijo-Hamano Terry Kwok Anna Roujeinikova Conformational analysis of isolated domains of Helicobacter pylori CagA.
description	The CagA protein of Helicobacter pylori is associated with increased virulence and gastric cancer risk. CagA is translocated into the host cell by a H. pylori type IV secretion system via mechanisms that are poorly understood. Translocated CagA interacts with numerous host factors, altering a variety of host signalling pathways. The recently determined crystal structure of C-terminally-truncated CagA indicated the presence of two domains: the smaller, flexible N-terminal domain and the larger, middle domain. In this study, we have investigated the conformation, oligomeric state and stability of the N-terminal, middle and glutamate-proline-isoleucine-tyrosine-alanine (EPIYA)-repeats domains. All three domains are monomeric, suggesting that the multimerisation of CagA observed in infected cells is likely to be mediated not by CagA itself but by its interacting partners. The middle and the C-terminal domains, but not the N-terminal domain, are capable of refolding spontaneously upon heat denaturation, lending support to the hypothesis that unfolded CagA is threaded C-terminus first through the type IV secretion channel with its N-terminal domain, which likely requires interactions with other domains to refold, being threaded last. Our findings also revealed that the C-terminal EPIYA-repeats domain of CagA exists in an intrinsically disordered premolten globule state with regions in PPII conformation--a feature that is shared by many scaffold proteins that bind multiple protein components of signalling pathways. Taken together, these results provide a deeper understanding of the physicochemical properties of CagA that underpin its complex cellular and oncogenic functions.
format	article
author	Amanda P Woon Abolghasem Tohidpour Hernan Alonso Yumiko Saijo-Hamano Terry Kwok Anna Roujeinikova
author_facet	Amanda P Woon Abolghasem Tohidpour Hernan Alonso Yumiko Saijo-Hamano Terry Kwok Anna Roujeinikova
author_sort	Amanda P Woon
title	Conformational analysis of isolated domains of Helicobacter pylori CagA.
title_short	Conformational analysis of isolated domains of Helicobacter pylori CagA.
title_full	Conformational analysis of isolated domains of Helicobacter pylori CagA.
title_fullStr	Conformational analysis of isolated domains of Helicobacter pylori CagA.
title_full_unstemmed	Conformational analysis of isolated domains of Helicobacter pylori CagA.
title_sort	conformational analysis of isolated domains of helicobacter pylori caga.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/9f14f6a09eed49eb84c834b795590d73
work_keys_str_mv	AT amandapwoon conformationalanalysisofisolateddomainsofhelicobacterpyloricaga AT abolghasemtohidpour conformationalanalysisofisolateddomainsofhelicobacterpyloricaga AT hernanalonso conformationalanalysisofisolateddomainsofhelicobacterpyloricaga AT yumikosaijohamano conformationalanalysisofisolateddomainsofhelicobacterpyloricaga AT terrykwok conformationalanalysisofisolateddomainsofhelicobacterpyloricaga AT annaroujeinikova conformationalanalysisofisolateddomainsofhelicobacterpyloricaga
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Conformational analysis of isolated domains of Helicobacter pylori CagA.

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