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| | ==Bordetella pertussis adenylate cyclase toxin transmembrane segment 411-490 in DPC micelles== | | ==Bordetella pertussis adenylate cyclase toxin transmembrane segment 411-490 in DPC micelles== |
| - | <StructureSection load='6rfm' size='340' side='right'caption='[[6rfm]], [[NMR_Ensembles_of_Models | 50 NMR models]]' scene=''> | + | <StructureSection load='6rfm' size='340' side='right'caption='[[6rfm]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6rfm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacterium_tussis-convulsivae"_lehmann_and_neumann_1927 "bacterium tussis-convulsivae" lehmann and neumann 1927]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RFM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6RFM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6rfm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bordetella_pertussis Bordetella pertussis]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RFM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RFM FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">cya, cyaA, BN118_0468 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=520 "Bacterium tussis-convulsivae" Lehmann and Neumann 1927])</td></tr> | + | </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=6rfm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rfm OCA], [https://pdbe.org/6rfm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rfm RCSB], [https://www.ebi.ac.uk/pdbsum/6rfm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rfm ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenylate_cyclase Adenylate cyclase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.6.1.1 4.6.1.1] </span></td></tr>
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6rfm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rfm OCA], [http://pdbe.org/6rfm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rfm RCSB], [http://www.ebi.ac.uk/pdbsum/6rfm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rfm ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CYAA_BORP1 CYAA_BORP1]] This adenylate cyclase belongs to a special class of bacterial toxin. It causes whooping cough by acting on mammalian cells by elevating cAMP-concentration and thus disrupts normal cell function.<ref>PMID:2905265</ref> | + | [https://www.uniprot.org/uniprot/CYAA_BORPE CYAA_BORPE] This adenylate cyclase belongs to a special class of bacterial toxin. It causes whooping cough by acting on mammalian cells by elevating cAMP-concentration and thus disrupts normal cell function. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacterium tussis-convulsivae lehmann and neumann 1927]] | |
| - | [[Category: Adenylate cyclase]] | |
| - | [[Category: Large Structures]] | |
| - | [[Category: Bumba, L]] | |
| - | [[Category: Masin, J]] | |
| - | [[Category: Veverka, V]] | |
| | [[Category: Bordetella pertussis]] | | [[Category: Bordetella pertussis]] |
| - | [[Category: Calcium binding]] | + | [[Category: Large Structures]] |
| - | [[Category: Membrane protein]] | + | [[Category: Bumba L]] |
| - | [[Category: Toxin]] | + | [[Category: Masin J]] |
| | + | [[Category: Veverka V]] |
| Structural highlights
Function
CYAA_BORPE This adenylate cyclase belongs to a special class of bacterial toxin. It causes whooping cough by acting on mammalian cells by elevating cAMP-concentration and thus disrupts normal cell function.
Publication Abstract from PubMed
Two distinct conformers of the adenylate cyclase toxin (CyaA) appear to accomplish its two parallel activities within target cell membrane. The translocating conformer would deliver the N-terminal adenylyl cyclase (AC) enzyme domain across plasma membrane into cytosol of cells, while the pore precursor conformer would assemble into oligomeric cation-selective pores and permeabilize cellular membrane. Both toxin activities then involve a membrane-interacting 'AC-to-Hly-linking segment' (residues 400 to 500). Here, we report the NMR structure of the corresponding CyaA411-490 polypeptide in dodecylphosphocholine micelles and show that it consists of two alpha-helices linked by an unrestrained loop. The N-terminal alpha-helix (Gly418 to His439) remained solvent accessible, while the C-terminal alpha-helix (His457 to Phe485) was fully enclosed within detergent micelles. CyaA411-490 weakly bound Ca(2+) ions (apparent KD 2.6 mM) and permeabilized negatively charged lipid vesicles. At high concentrations (10 muM) the CyaA411-490 polypeptide formed stable conductance units in artificial lipid bilayers with applied voltage, suggesting its possible transmembrane orientation in the membrane-inserted toxin. Mutagenesis revealed that two clusters of negatively charged residues within the 'AC-to-Hly-linking segment' (Glu419 to Glu432 and Asp445 to Glu448) regulate the balance between the AC domain translocating and pore-forming capacities of CyaA in function of calcium concentration.
Negative charge of the AC-to-Hly linking segment modulates calcium-dependent membrane activities of Bordetella adenylate cyclase toxin.,Sukova A, Bumba L, Srb P, Veverka V, Stanek O, Holubova J, Chmelik J, Fiser R, Sebo P, Masin J Biochim Biophys Acta Biomembr. 2020 Sep 1;1862(9):183310. doi:, 10.1016/j.bbamem.2020.183310. Epub 2020 Apr 22. PMID:32333856[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sukova A, Bumba L, Srb P, Veverka V, Stanek O, Holubova J, Chmelik J, Fiser R, Sebo P, Masin J. Negative charge of the AC-to-Hly linking segment modulates calcium-dependent membrane activities of Bordetella adenylate cyclase toxin. Biochim Biophys Acta Biomembr. 2020 Sep 1;1862(9):183310. doi:, 10.1016/j.bbamem.2020.183310. Epub 2020 Apr 22. PMID:32333856 doi:http://dx.doi.org/10.1016/j.bbamem.2020.183310
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