7o85: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==== | ==Anthrax toxin prepore in complex with the neutralizing Fab cAb29== | ||
<StructureSection load='7o85' size='340' side='right'caption='[[7o85]]' scene=''> | <StructureSection load='7o85' size='340' side='right'caption='[[7o85]], [[Resolution|resolution]] 3.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7o85]] is a 21 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7O85 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7O85 FirstGlance]. <br> | ||
</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=7o85 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o85 OCA], [https://pdbe.org/7o85 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o85 RCSB], [https://www.ebi.ac.uk/pdbsum/7o85 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o85 ProSAT]</span></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]] 3.3Å</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7o85 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o85 OCA], [https://pdbe.org/7o85 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o85 RCSB], [https://www.ebi.ac.uk/pdbsum/7o85 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o85 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://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. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Anthrax infection is associated with severe illness and high mortality. Protective antigen (PA) is the central component of the anthrax toxin, which is one of two major virulence factors of Bacillus anthracis, the causative agent of anthrax disease. Upon endocytosis, PA opens a pore in the membranes of endosomes, through which the cytotoxic enzymes of the toxin are extruded. The PA pore is formed by a cooperative conformational change in which the membrane-penetrating loops of PA associate, forming a hydrophobic rim that pierces the membrane. Due to its crucial role in anthrax progression, PA is an important target for monoclonal antibody-based therapy. cAb29 is a highly effective neutralizing antibody against PA. Here, the cryo-EM structure of PA in complex with the Fab portion of cAb29 was determined. It was found that cAb29 neutralizes the toxin by clamping the membrane-penetrating loop of PA to the static surface-exposed loop of the D3 domain of the same subunit, thereby preventing pore formation. These results provide the structural basis for the antibody-based neutralization of PA and bring into focus the membrane-penetrating loop of PA as a target for the development of better anti-anthrax vaccines. | |||
Neutralization of the anthrax toxin by antibody-mediated stapling of its membrane-penetrating loop.,Hoelzgen F, Zalk R, Alcalay R, Cohen-Schwartz S, Garau G, Shahar A, Mazor O, Frank GA Acta Crystallogr D Struct Biol. 2021 Sep 1;77(Pt 9):1197-1205. doi: , 10.1107/S2059798321007816. Epub 2021 Aug 25. PMID:34473089<ref>PMID:34473089</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7o85" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Bacillus anthracis]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mus musculus]] | ||
[[Category: Alcalay R]] | |||
[[Category: Cohen-Schwartz S]] | |||
[[Category: Frank GA]] | |||
[[Category: Garau G]] | |||
[[Category: Hoelzgen F]] | |||
[[Category: Mazor O]] | |||
[[Category: Shahar A]] | |||
[[Category: Zalk R]] | |||
Latest revision as of 14:16, 23 October 2024
Anthrax toxin prepore in complex with the neutralizing Fab cAb29Anthrax toxin prepore in complex with the neutralizing Fab cAb29
Structural highlights
FunctionPAG_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. Publication Abstract from PubMedAnthrax infection is associated with severe illness and high mortality. Protective antigen (PA) is the central component of the anthrax toxin, which is one of two major virulence factors of Bacillus anthracis, the causative agent of anthrax disease. Upon endocytosis, PA opens a pore in the membranes of endosomes, through which the cytotoxic enzymes of the toxin are extruded. The PA pore is formed by a cooperative conformational change in which the membrane-penetrating loops of PA associate, forming a hydrophobic rim that pierces the membrane. Due to its crucial role in anthrax progression, PA is an important target for monoclonal antibody-based therapy. cAb29 is a highly effective neutralizing antibody against PA. Here, the cryo-EM structure of PA in complex with the Fab portion of cAb29 was determined. It was found that cAb29 neutralizes the toxin by clamping the membrane-penetrating loop of PA to the static surface-exposed loop of the D3 domain of the same subunit, thereby preventing pore formation. These results provide the structural basis for the antibody-based neutralization of PA and bring into focus the membrane-penetrating loop of PA as a target for the development of better anti-anthrax vaccines. Neutralization of the anthrax toxin by antibody-mediated stapling of its membrane-penetrating loop.,Hoelzgen F, Zalk R, Alcalay R, Cohen-Schwartz S, Garau G, Shahar A, Mazor O, Frank GA Acta Crystallogr D Struct Biol. 2021 Sep 1;77(Pt 9):1197-1205. doi: , 10.1107/S2059798321007816. Epub 2021 Aug 25. PMID:34473089[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||