schliessen

Filtern

 

Bibliotheken

Characterization of Mycobacterium tuberculosis EsxA membrane insertion: roles of N- and C-terminal flexible arms and central helix-turn-helix motif

EsxA (ESAT-6), an important virulence factor of Mycobacterium tuberculosis, plays an essential role in phagosome rupture and bacterial cytosolic translocation within host macrophages. Our previous study showed that EsxA exhibits a unique membrane-interacting activity that is not found in its ortholo... Full description

Journal Title: The Journal of biological chemistry 13 March 2015, Vol.290(11), pp.7314-22
Main Author: Ma, Yue
Other Authors: Keil, Verena , Sun, Jianjun
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1083-351X ; PMID: 25645924 Version:1 ; DOI: 10.1074/jbc.M114.622076
Link: http://pubmed.gov/25645924
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: medline25645924
title: Characterization of Mycobacterium tuberculosis EsxA membrane insertion: roles of N- and C-terminal flexible arms and central helix-turn-helix motif
format: Article
creator:
  • Ma, Yue
  • Keil, Verena
  • Sun, Jianjun
subjects:
  • Conformational Change
  • Esat-6
  • Esxa
  • Membrane
  • Mycobacterium Tuberculosis
  • Pathogenesis
  • Virulence Factor
  • Host-Pathogen Interactions
  • Antigens, Bacterial -- Metabolism
  • Bacterial Proteins -- Metabolism
  • Mycobacterium Tuberculosis -- Physiology
  • Tuberculosis -- Metabolism
  • Virulence Factors -- Metabolism
ispartof: The Journal of biological chemistry, 13 March 2015, Vol.290(11), pp.7314-22
description: EsxA (ESAT-6), an important virulence factor of Mycobacterium tuberculosis, plays an essential role in phagosome rupture and bacterial cytosolic translocation within host macrophages. Our previous study showed that EsxA exhibits a unique membrane-interacting activity that is not found in its ortholog from nonpathogenic Mycobacterium smegmatis. However, the molecular mechanism of EsxA membrane insertion remains unknown. In this study, we generated truncated EsxA proteins with deletions of the N- and/or C-terminal flexible arm. Using a fluorescence-based liposome leakage assay, we found that both the N- and C-terminal arms were required for membrane disruption. Moreover, we found that, upon acidification, EsxA converted into a more organized structure with increased α-helical content, which was evidenced by CD analysis and intrinsic tryptophan fluorescence. Finally, using an environmentally sensitive fluorescent dye, we obtained direct evidence that the central helix-turn-helix motif of EsxA...
language: eng
source:
identifier: E-ISSN: 1083-351X ; PMID: 25645924 Version:1 ; DOI: 10.1074/jbc.M114.622076
fulltext: fulltext
issn:
  • 1083351X
  • 1083-351X
url: Link


@attributes
ID1566700058
RANK0.07
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
LOCALfalse
PrimoNMBib
record
control
sourcerecordid25645924
sourceidmedline
recordidTN_medline25645924
sourceformatXML
sourcesystemPC
pqid1663899063
display
typearticle
titleCharacterization of Mycobacterium tuberculosis EsxA membrane insertion: roles of N- and C-terminal flexible arms and central helix-turn-helix motif
creatorMa, Yue ; Keil, Verena ; Sun, Jianjun
ispartofThe Journal of biological chemistry, 13 March 2015, Vol.290(11), pp.7314-22
identifier
subjectConformational Change ; Esat-6 ; Esxa ; Membrane ; Mycobacterium Tuberculosis ; Pathogenesis ; Virulence Factor ; Host-Pathogen Interactions ; Antigens, Bacterial -- Metabolism ; Bacterial Proteins -- Metabolism ; Mycobacterium Tuberculosis -- Physiology ; Tuberculosis -- Metabolism ; Virulence Factors -- Metabolism
descriptionEsxA (ESAT-6), an important virulence factor of Mycobacterium tuberculosis, plays an essential role in phagosome rupture and bacterial cytosolic translocation within host macrophages. Our previous study showed that EsxA exhibits a unique membrane-interacting activity that is not found in its ortholog from nonpathogenic Mycobacterium smegmatis. However, the molecular mechanism of EsxA membrane insertion remains unknown. In this study, we generated truncated EsxA proteins with deletions of the N- and/or C-terminal flexible arm. Using a fluorescence-based liposome leakage assay, we found that both the N- and C-terminal arms were required for membrane disruption. Moreover, we found that, upon acidification, EsxA converted into a more organized structure with increased α-helical content, which was evidenced by CD analysis and intrinsic tryptophan fluorescence. Finally, using an environmentally sensitive fluorescent dye, we obtained direct evidence that the central helix-turn-helix motif of EsxA...
languageeng
source
version3
lds50peer_reviewed
links
openurl$$Topenurl_article
backlink$$Uhttp://pubmed.gov/25645924$$EView_this_record_in_MEDLINE/PubMed
openurlfulltext$$Topenurlfull_article
addlink$$Uhttp://exlibris-pub.s3.amazonaws.com/aboutMedline.html$$EView_the_MEDLINE/PubMed_Copyright_Statement
search
creatorcontrib
0Ma, Yue
1Keil, Verena
2Sun, Jianjun
titleCharacterization of Mycobacterium tuberculosis EsxA membrane insertion: roles of N- and C-terminal flexible arms and central helix-turn-helix motif
descriptionEsxA (ESAT-6), an important virulence factor of Mycobacterium tuberculosis, plays an essential role in phagosome rupture and bacterial cytosolic translocation within host macrophages. Our previous study showed that EsxA exhibits a unique membrane-interacting activity that is not found in its ortholog from nonpathogenic Mycobacterium smegmatis. However, the molecular mechanism of EsxA membrane insertion remains unknown. In this study, we generated truncated EsxA proteins with deletions of the N- and/or C-terminal flexible arm. Using a fluorescence-based liposome leakage assay, we found that both the N- and C-terminal arms were required for membrane disruption. Moreover, we found that, upon acidification, EsxA converted into a more organized structure with increased α-helical content, which was evidenced by CD analysis and intrinsic tryptophan fluorescence. Finally, using an environmentally sensitive fluorescent dye, we obtained direct evidence that the central helix-turn-helix motif of EsxA...
subject
0Conformational Change
1Esat-6
2Esxa
3Membrane
4Mycobacterium Tuberculosis
5Pathogenesis
6Virulence Factor
7Host-Pathogen Interactions
8Antigens, Bacterial -- Metabolism
9Bacterial Proteins -- Metabolism
10Mycobacterium Tuberculosis -- Physiology
11Tuberculosis -- Metabolism
12Virulence Factors -- Metabolism
general
025645924
1English
2MEDLINE/PubMed (U.S. National Library of Medicine)
310.1074/jbc.M114.622076
4MEDLINE/PubMed (NLM)
sourceidmedline
recordidmedline25645924
issn
01083351X
11083-351X
rsrctypearticle
creationdate2015
addtitleThe Journal of biological chemistry
searchscope
0medline
1nlm_medline
2MEDLINE
scope
0medline
1nlm_medline
2MEDLINE
lsr4120150313
citationpf 7314 vol 290 issue 11
startdate20150313
enddate20150313
lsr30VSR-Enriched:[pages, pqid]
sort
titleCharacterization of Mycobacterium tuberculosis EsxA membrane insertion: roles of N- and C-terminal flexible arms and central helix-turn-helix motif
authorMa, Yue ; Keil, Verena ; Sun, Jianjun
creationdate20150313
lso0120150313
facets
frbrgroupid9151041988274008087
frbrtype5
newrecords20190701
languageeng
creationdate2015
topic
0Conformational Change
1Esat-6
2Esxa
3Membrane
4Mycobacterium Tuberculosis
5Pathogenesis
6Virulence Factor
7Host-Pathogen Interactions
8Antigens, Bacterial–Metabolism
9Bacterial Proteins–Metabolism
10Mycobacterium Tuberculosis–Physiology
11Tuberculosis–Metabolism
12Virulence Factors–Metabolism
collectionMEDLINE/PubMed (NLM)
prefilterarticles
rsrctypearticles
creatorcontrib
0Ma, Yue
1Keil, Verena
2Sun, Jianjun
jtitleJournal Of Biological Chemistry
toplevelpeer_reviewed
delivery
delcategoryRemote Search Resource
fulltextfulltext
addata
aulast
0Ma
1Keil
2Sun
aufirst
0Yue
1Verena
2Jianjun
au
0Ma, Yue
1Keil, Verena
2Sun, Jianjun
atitleCharacterization of Mycobacterium tuberculosis EsxA membrane insertion: roles of N- and C-terminal flexible arms and central helix-turn-helix motif
jtitleThe Journal of biological chemistry
risdate20150313
volume290
issue11
spage7314
pages7314-7322
issn0021-9258
eissn1083-351X
formatjournal
genrearticle
ristypeJOUR
abstractEsxA (ESAT-6), an important virulence factor of Mycobacterium tuberculosis, plays an essential role in phagosome rupture and bacterial cytosolic translocation within host macrophages. Our previous study showed that EsxA exhibits a unique membrane-interacting activity that is not found in its ortholog from nonpathogenic Mycobacterium smegmatis. However, the molecular mechanism of EsxA membrane insertion remains unknown. In this study, we generated truncated EsxA proteins with deletions of the N- and/or C-terminal flexible arm. Using a fluorescence-based liposome leakage assay, we found that both the N- and C-terminal arms were required for membrane disruption. Moreover, we found that, upon acidification, EsxA converted into a more organized structure with increased α-helical content, which was evidenced by CD analysis and intrinsic tryptophan fluorescence. Finally, using an environmentally sensitive fluorescent dye, we obtained direct evidence that the central helix-turn-helix motif of EsxA...
doi10.1074/jbc.M114.622076
pmid25645924
date2015-03-13