6hhu: Difference between revisions
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The | ==Structure of the Bacillus anthracis Sap S-layer assembly domain== | ||
<StructureSection load='6hhu' size='340' side='right'caption='[[6hhu]], [[Resolution|resolution]] 2.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6hhu]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HHU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HHU FirstGlance]. <br> | |||
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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=6hhu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hhu OCA], [http://pdbe.org/6hhu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hhu RCSB], [http://www.ebi.ac.uk/pdbsum/6hhu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hhu ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/SLAP1_BACAN SLAP1_BACAN]] The S-layer is a paracrystalline mono-layered assembly of proteins which coat the surface of bacteria. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Anthrax is an ancient and deadly disease caused by the spore-forming bacterial pathogen Bacillus anthracis. At present, anthrax mostly affects wildlife and livestock, although it remains a concern for human public health-primarily for people who handle contaminated animal products and as a bioterrorism threat due to the high resilience of spores, a high fatality rate of cases and the lack of a civilian vaccination programme(1,2). The cell surface of B. anthracis is covered by a protective paracrystalline monolayer-known as surface layer or S-layer-that is composed of the S-layer proteins Sap or EA1. Here, we generate nanobodies to inhibit the self-assembly of Sap, determine the structure of the Sap S-layer assembly domain (Sap(AD)) and show that the disintegration of the S-layer attenuates the growth of B. anthracis and the pathology of anthrax in vivo. Sap(AD) comprises six beta-sandwich domains that fold and support the formation of S-layers independently of calcium. Sap-inhibitory nanobodies prevented the assembly of Sap and depolymerized existing Sap S-layers in vitro. In vivo, nanobody-mediated disruption of the Sap S-layer resulted in severe morphological defects and attenuated bacterial growth. Subcutaneous delivery of Sap inhibitory nanobodies cleared B. anthracis infection and prevented lethality in a mouse model of anthrax disease. These findings highlight disruption of S-layer integrity as a mechanism that has therapeutic potential in S-layer-carrying pathogens. | |||
Structure of S-layer protein Sap reveals a mechanism for therapeutic intervention in anthrax.,Fioravanti A, Van Hauwermeiren F, Van der Verren SE, Jonckheere W, Goncalves A, Pardon E, Steyaert J, De Greve H, Lamkanfi M, Remaut H Nat Microbiol. 2019 Jul 15. pii: 10.1038/s41564-019-0499-1. doi:, 10.1038/s41564-019-0499-1. PMID:31308522<ref>PMID:31308522</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6hhu" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Fioravanti, A]] | |||
[[Category: Remaut, H]] | [[Category: Remaut, H]] | ||
[[Category: | [[Category: Bacterial cell surface]] | ||
[[Category: Exoskeleton]] | |||
[[Category: S-layer]] | |||
[[Category: Structural protein]] | |||
Revision as of 09:08, 24 July 2019
Structure of the Bacillus anthracis Sap S-layer assembly domainStructure of the Bacillus anthracis Sap S-layer assembly domain
Structural highlights
Function[SLAP1_BACAN] The S-layer is a paracrystalline mono-layered assembly of proteins which coat the surface of bacteria. Publication Abstract from PubMedAnthrax is an ancient and deadly disease caused by the spore-forming bacterial pathogen Bacillus anthracis. At present, anthrax mostly affects wildlife and livestock, although it remains a concern for human public health-primarily for people who handle contaminated animal products and as a bioterrorism threat due to the high resilience of spores, a high fatality rate of cases and the lack of a civilian vaccination programme(1,2). The cell surface of B. anthracis is covered by a protective paracrystalline monolayer-known as surface layer or S-layer-that is composed of the S-layer proteins Sap or EA1. Here, we generate nanobodies to inhibit the self-assembly of Sap, determine the structure of the Sap S-layer assembly domain (Sap(AD)) and show that the disintegration of the S-layer attenuates the growth of B. anthracis and the pathology of anthrax in vivo. Sap(AD) comprises six beta-sandwich domains that fold and support the formation of S-layers independently of calcium. Sap-inhibitory nanobodies prevented the assembly of Sap and depolymerized existing Sap S-layers in vitro. In vivo, nanobody-mediated disruption of the Sap S-layer resulted in severe morphological defects and attenuated bacterial growth. Subcutaneous delivery of Sap inhibitory nanobodies cleared B. anthracis infection and prevented lethality in a mouse model of anthrax disease. These findings highlight disruption of S-layer integrity as a mechanism that has therapeutic potential in S-layer-carrying pathogens. Structure of S-layer protein Sap reveals a mechanism for therapeutic intervention in anthrax.,Fioravanti A, Van Hauwermeiren F, Van der Verren SE, Jonckheere W, Goncalves A, Pardon E, Steyaert J, De Greve H, Lamkanfi M, Remaut H Nat Microbiol. 2019 Jul 15. pii: 10.1038/s41564-019-0499-1. doi:, 10.1038/s41564-019-0499-1. PMID:31308522[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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