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| | <SX load='6uzd' size='340' side='right' viewer='molstar' caption='[[6uzd]], [[Resolution|resolution]] 3.40Å' scene=''> | | <SX load='6uzd' size='340' side='right' viewer='molstar' caption='[[6uzd]], [[Resolution|resolution]] 3.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6uzd]] is a 9 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UZD OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6UZD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6uzd]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UZD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UZD FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6uzb|6uzb]], [[6psn|6psn]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></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>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6uzd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uzd OCA], [https://pdbe.org/6uzd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uzd RCSB], [https://www.ebi.ac.uk/pdbsum/6uzd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uzd ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6uzd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uzd OCA], [http://pdbe.org/6uzd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6uzd RCSB], [http://www.ebi.ac.uk/pdbsum/6uzd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6uzd ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PAG_BACAN PAG_BACAN]] One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. PA binds to a receptor (ATR) in sensitive eukaryotic cells, thereby facilitating the translocation of the enzymatic toxin components, edema factor and lethal factor, across the target cell membrane. PA associated with LF causes death when injected, PA associated with EF produces edema. PA induces immunity to infection with anthrax. [[http://www.uniprot.org/uniprot/CYAA_BACAN CYAA_BACAN]] One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. EF is a calmodulin-dependent adenylyl cyclase that, when associated with PA, causes edema. EF is not toxic by itself and it is required for the survival of germinated spores within macrophages at the early stages of infection. Provokes dramatic elevation of intracellular cAMP levels in the host. | + | [https://www.uniprot.org/uniprot/CYAA_BACAN CYAA_BACAN] One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. EF is a calmodulin-dependent adenylyl cyclase that, when associated with PA, causes edema. EF is not toxic by itself and it is required for the survival of germinated spores within macrophages at the early stages of infection. Provokes dramatic elevation of intracellular cAMP levels in the host. |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Following assembly, the anthrax protective antigen (PA) forms an oligomeric translocon that unfolds and translocates either its lethal factor (LF) or edema factor (EF) into the host cell. Here, we report the cryo-EM structures of heptameric PA channels with partially unfolded LF and EF at 4.6 and 3.1-A resolution, respectively. The first alpha helix and beta strand of LF and EF unfold and dock into a deep amphipathic cleft, called the alpha clamp, which resides at the interface of two PA monomers. The alpha-clamp-helix interactions exhibit structural plasticity when comparing the structures of lethal and edema toxins. EF undergoes a largescale conformational rearrangement when forming the complex with the channel. A critical loop in the PA binding interface is displaced for about 4 A, leading to the weakening of the binding interface prior to translocation. These structures provide key insights into the molecular mechanisms of translocation-coupled protein unfolding and translocation.
| + | |
| | | | |
| - | Atomic structures of anthrax toxin protective antigen channels bound to partially unfolded lethal and edema factors.,Hardenbrook NJ, Liu S, Zhou K, Ghosal K, Hong Zhou Z, Krantz BA Nat Commun. 2020 Feb 11;11(1):840. doi: 10.1038/s41467-020-14658-6. PMID:32047164<ref>PMID:32047164</ref>
| + | ==See Also== |
| - | | + | *[[3D Adenylyl cyclase 3D structures|3D Adenylyl cyclase 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6uzd" style="background-color:#fffaf0;"></div>
| + | |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Adenylate cyclase]] | + | [[Category: Bacillus anthracis]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hardenbrook, N J]] | + | [[Category: Hardenbrook NJ]] |
| - | [[Category: Krantz, B A]] | + | [[Category: Krantz BA]] |
| - | [[Category: Liu, S]] | + | [[Category: Liu S]] |
| - | [[Category: Zhou, K]] | + | [[Category: Zhou K]] |
| - | [[Category: Zhou, Z H]] | + | [[Category: Zhou ZH]] |
| - | [[Category: Anthrax toxin]]
| + | |
| - | [[Category: Edema factor]]
| + | |
| - | [[Category: Protective antigen]]
| + | |
| - | [[Category: Translocase]]
| + | |
