View source for 7rah


==Adenylate cyclase toxin RTX domain fragment bound to M1H5 Fab and M2B10 Fab==
<StructureSection load='7rah' size='340' side='right'caption='[[7rah]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7rah]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Bordetella_pertussis Bordetella pertussis] 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=7RAH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RAH FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</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>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=7rah FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rah OCA], [https://pdbe.org/7rah PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rah RCSB], [https://www.ebi.ac.uk/pdbsum/7rah PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rah ProSAT]</span></td></tr>
</table>
== Function ==
[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.
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== Publication Abstract from PubMed ==
RTX leukotoxins are a diverse family of prokaryotic virulence factors that are secreted by the type 1 secretion system (T1SS) and target leukocytes to subvert host defenses. T1SS substrates all contain a C-terminal RTX domain that mediates recruitment to the T1SS and drives secretion via a Brownian ratchet mechanism. Neutralizing antibodies against the Bordetella pertussis adenylate cyclase toxin, an RTX leukotoxin essential for B. pertussis colonization, have been shown to target the RTX domain and prevent binding to the alphaMbeta2 integrin receptor. Knowledge of the mechanisms by which antibodies bind and neutralize RTX leukotoxins is required to inform structure-based design of bacterial vaccines, however, no structural data are available for antibody binding to any T1SS substrate. Here, we determine the crystal structure of an engineered RTX domain fragment containing the alphaMbeta2-binding site bound to two neutralizing antibodies. Notably, the receptor-blocking antibodies bind to the linker regions of RTX blocks I-III, suggesting they are key neutralization-sensitive sites within the RTX domain and are likely involved in binding the alphaMbeta2 receptor. As the engineered RTX fragment contained these key epitopes, we assessed its immunogenicity in mice and showed that it elicits similar neutralizing antibody titers to the full RTX domain. The results from these studies will support the development of bacterial vaccines targeting RTX leukotoxins, as well as next-generation B. pertussis vaccines.

Structural basis for antibody binding to adenylate cyclase toxin reveals RTX linkers as neutralization-sensitive epitopes.,Goldsmith JA, DiVenere AM, Maynard JA, McLellan JS PLoS Pathog. 2021 Sep 21;17(9):e1009920. doi: 10.1371/journal.ppat.1009920. , eCollection 2021 Sep. PMID:34547035<ref>PMID:34547035</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7rah" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Bordetella pertussis]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Goldsmith JA]]
[[Category: McLellan JS]]