6gif

From Proteopedia

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Current revision

AapA1 V26A toxin from helicobacter pylori 26695

Structural highlights

6gif is a 1 chain structure with sequence from Helicobacter pylori SS1. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

AAPA1_HELPY May be involved in response to oxidative stress (Probable). Toxic component of a type I toxin-antitoxin (TA) system. When overexpression is induced in situ in the absence of its cognate antisense RNA antitoxin IsoA1 it leads to cell growth arrest and cell death without lysis. Neutralized by IsoA1 RNA which forms an extensive duplex with the mRNA (PubMed:28077560, PubMed:31476357, PubMed:33229580). Binds artificial prokaryotic and eukaryotic lipid membranes, with 30-fold higher affinity for prokaryotic membranes. Molecular dynamics suggests the peptide penetrates the membrane leading to lipid reorganization and thinning of the bilayer (PubMed:31476357). Induction of toxin in the absence of antitoxin RNA causes a fast conversion of cells from spiral-shaped to coccoid forms; cells have no visible membrane defects and resemble wild-type 'aging coccoids'. Toxin causes a moderate decrease in membrane potential and ATP content and alterations in peptidoglycan muropeptide abundance; GlcNAc-MurNAc dipeptides increase while GlcNAc-MurNAc tripeptides decrease (i.e. a faster phenocopy of cell aging). Deletion of all 6 AapA/IsoA TA loci in strain B128 leads to slower than wild-type conversion of H2O2-treated cells to the coccoid form. This suggests oxidative stress triggers coccoid transformation via these type I TA systems, although other factors eventually drive the morphology change (PubMed:33229580).^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

BACKGROUND: We previously reported the identification of the aapA1/IsoA1 locus as part of a new family of toxin-antitoxin (TA) systems in the human pathogen Helicobacter pylori. AapA1 belongs to type I TA bacterial toxins, and both its mechanism of action towards the membrane and toxicity features are still unclear. METHODS: The biochemical characterization of the AapA1 toxic peptide was carried out using plasmid-borne expression and mutational approaches to follow its toxicity and localization. Biophysical properties of the AapA1 interaction with lipid membranes were studied by solution and solid-state NMR spectroscopy, plasmon waveguide resonance (PWR) and molecular modeling. RESULTS: We show that despite a low hydrophobic index, this toxin has a nanomolar affinity to the prokaryotic membrane. NMR spectroscopy reveals that the AapA1 toxin is structurally organized into three distinct domains: a positively charged disordered N-terminal domain (D), a single alpha-helix (H), and a basic C-terminal domain (R). The R domain interacts and destabilizes the membrane, while the H domain adopts a transmembrane conformation. These results were confirmed by alanine scanning of the minimal sequence required for toxicity. CONCLUSION: Our results have shown that specific amino acid residues along the H domain, as well as the R domain, are essential for the toxicity of the AapA1 toxin. GENERAL SIGNIFICANCE: Untangling and understanding the mechanism of action of small membrane-targeting toxins are difficult, but nevertheless contributes to a promising search and development of new antimicrobial drugs.

Structural insights into the AapA1 toxin of Helicobacter pylori.,Korkut DN, Alves ID, Vogel A, Chabas S, Sharma CM, Martinez D, Loquet A, Salgado GF, Darfeuille F Biochim Biophys Acta Gen Subj. 2020 Jan;1864(1):129423. doi:, 10.1016/j.bbagen.2019.129423. Epub 2019 Aug 30. PMID:31476357^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Arnion H, Korkut DN, Masachis Gelo S, Chabas S, Reignier J, Iost I, Darfeuille F. Mechanistic insights into type I toxin antitoxin systems in Helicobacter pylori: the importance of mRNA folding in controlling toxin expression. Nucleic Acids Res. 2017 May 5;45(8):4782-4795. PMID:28077560 doi:10.1093/nar/gkw1343
↑ Korkut DN, Alves ID, Vogel A, Chabas S, Sharma CM, Martinez D, Loquet A, Salgado GF, Darfeuille F. Structural insights into the AapA1 toxin of Helicobacter pylori. Biochim Biophys Acta Gen Subj. 2020 Jan;1864(1):129423. doi:, 10.1016/j.bbagen.2019.129423. Epub 2019 Aug 30. PMID:31476357 doi:http://dx.doi.org/10.1016/j.bbagen.2019.129423
↑ El Mortaji L, Tejada-Arranz A, Rifflet A, Boneca IG, Pehau-Arnaudet G, Radicella JP, Marsin S, De Reuse H. A peptide of a type I toxin-antitoxin system induces Helicobacter pylori morphological transformation from spiral shape to coccoids. Proc Natl Acad Sci U S A. 2020 Dec 8;117(49):31398-31409. PMID:33229580 doi:10.1073/pnas.2016195117
↑ El Mortaji L, Tejada-Arranz A, Rifflet A, Boneca IG, Pehau-Arnaudet G, Radicella JP, Marsin S, De Reuse H. A peptide of a type I toxin-antitoxin system induces Helicobacter pylori morphological transformation from spiral shape to coccoids. Proc Natl Acad Sci U S A. 2020 Dec 8;117(49):31398-31409. PMID:33229580 doi:10.1073/pnas.2016195117
↑ Korkut DN, Alves ID, Vogel A, Chabas S, Sharma CM, Martinez D, Loquet A, Salgado GF, Darfeuille F. Structural insights into the AapA1 toxin of Helicobacter pylori. Biochim Biophys Acta Gen Subj. 2020 Jan;1864(1):129423. doi:, 10.1016/j.bbagen.2019.129423. Epub 2019 Aug 30. PMID:31476357 doi:http://dx.doi.org/10.1016/j.bbagen.2019.129423

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6gif"

Categories: Helicobacter pylori SS1 | Large Structures | Korkut DN | Salgado G

@@ Line 1: / Line 1: @@
 ==AapA1 V26A toxin from helicobacter pylori 26695==
-<StructureSection load='6gif' size='340' side='right'caption='[[6gif]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
+<StructureSection load='6gif' size='340' side='right'caption='[[6gif]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6gif]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GIF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GIF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6gif]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Helicobacter_pylori_SS1 Helicobacter pylori SS1]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GIF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6GIF FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6gif FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gif OCA], [http://pdbe.org/6gif PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gif RCSB], [http://www.ebi.ac.uk/pdbsum/6gif PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gif ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6gif FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gif OCA], [https://pdbe.org/6gif PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6gif RCSB], [https://www.ebi.ac.uk/pdbsum/6gif PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6gif ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/AAPA1_HELPY AAPA1_HELPY] May be involved in response to oxidative stress (Probable). Toxic component of a type I toxin-antitoxin (TA) system. When overexpression is induced in situ in the absence of its cognate antisense RNA antitoxin IsoA1 it leads to cell growth arrest and cell death without lysis. Neutralized by IsoA1 RNA which forms an extensive duplex with the mRNA (PubMed:28077560, PubMed:31476357, PubMed:33229580). Binds artificial prokaryotic and eukaryotic lipid membranes, with 30-fold higher affinity for prokaryotic membranes. Molecular dynamics suggests the peptide penetrates the membrane leading to lipid reorganization and thinning of the bilayer (PubMed:31476357). Induction of toxin in the absence of antitoxin RNA causes a fast conversion of cells from spiral-shaped to coccoid forms; cells have no visible membrane defects and resemble wild-type 'aging coccoids'. Toxin causes a moderate decrease in membrane potential and ATP content and alterations in peptidoglycan muropeptide abundance; GlcNAc-MurNAc dipeptides increase while GlcNAc-MurNAc tripeptides decrease (i.e. a faster phenocopy of cell aging). Deletion of all 6 AapA/IsoA TA loci in strain B128 leads to slower than wild-type conversion of H2O2-treated cells to the coccoid form. This suggests oxidative stress triggers coccoid transformation via these type I TA systems, although other factors eventually drive the morphology change (PubMed:33229580).<ref>PMID:28077560</ref> <ref>PMID:31476357</ref> <ref>PMID:33229580</ref> <ref>PMID:33229580</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 22: @@
 __TOC__
 </StructureSection>
+[[Category: Helicobacter pylori SS1]]
 [[Category: Large Structures]]
-[[Category: Korkut, D N]]
+[[Category: Korkut DN]]
-[[Category: Salgado, G]]
+[[Category: Salgado G]]
-[[Category: Aapa1 v26a toxin from helicobacter pylori 26695]]
-[[Category: Toxin]]

6gif

From Proteopedia

Current revision

AapA1 V26A toxin from helicobacter pylori 26695

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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