This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1xez
From Proteopedia
(New page: 200px<br /><applet load="1xez" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xez, resolution 2.3Å" /> '''Crystal Structure Of ...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1xez.gif|left|200px]]<br /><applet load="1xez" size=" | + | [[Image:1xez.gif|left|200px]]<br /><applet load="1xez" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1xez, resolution 2.3Å" /> | caption="1xez, resolution 2.3Å" /> | ||
'''Crystal Structure Of The Vibrio Cholerae Cytolysin (HlyA) Pro-Toxin With Octylglucoside Bound'''<br /> | '''Crystal Structure Of The Vibrio Cholerae Cytolysin (HlyA) Pro-Toxin With Octylglucoside Bound'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Pathogenic Vibrio cholerae secrete V. cholerae cytolysin (VCC), an 80 kDa | + | Pathogenic Vibrio cholerae secrete V. cholerae cytolysin (VCC), an 80 kDa pro-toxin that assembles into an oligomeric pore on target cell membranes following proteolytic cleavage and interaction with cell surface receptors. To gain insight into the activation and targeting activities of VCC, we solved the crystal structure of the pro-toxin at 2.3A by X-ray diffraction. The core cytolytic domain of VCC shares a fold similar to the staphylococcal pore-forming toxins, but in VCC an amino-terminal pro-domain and two carboxy-terminal lectin domains decorate the cytolytic domain. The pro-domain masks a protomer surface that likely participates in inter-protomer interactions in the cytolytic oligomer, thereby explaining why proteolytic cleavage and movement of the pro-domain is necessary for toxin activation. A single beta-octyl glucoside molecule outlines a possible receptor binding site on one lectin domain, and removal of this domain leads to a tenfold decrease in lytic activity toward rabbit erythrocytes. VCC activated by proteolytic cleavage assembles into an oligomeric species upon addition of soybean asolectin/cholesterol liposomes and this oligomer was purified in detergent micelles. Analytical ultracentrifugation and crystallographic analysis indicate that the resulting VCC oligomer is a heptamer. Taken together, these studies define the architecture of a pore forming toxin and associated lectin domains, confirm the stoichiometry of the assembled oligomer as heptameric, and suggest a common mechanism of assembly for staphylococcal and Vibrio cytolytic toxins. |
==About this Structure== | ==About this Structure== | ||
| - | 1XEZ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Vibrio_cholerae Vibrio cholerae] with BOG as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1XEZ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Vibrio_cholerae Vibrio cholerae] with <scene name='pdbligand=BOG:'>BOG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XEZ OCA]. |
==Reference== | ==Reference== | ||
| Line 24: | Line 24: | ||
[[Category: water-soluble monomer]] | [[Category: water-soluble monomer]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:54:03 2008'' |
Revision as of 13:54, 21 February 2008
|
Crystal Structure Of The Vibrio Cholerae Cytolysin (HlyA) Pro-Toxin With Octylglucoside Bound
Overview
Pathogenic Vibrio cholerae secrete V. cholerae cytolysin (VCC), an 80 kDa pro-toxin that assembles into an oligomeric pore on target cell membranes following proteolytic cleavage and interaction with cell surface receptors. To gain insight into the activation and targeting activities of VCC, we solved the crystal structure of the pro-toxin at 2.3A by X-ray diffraction. The core cytolytic domain of VCC shares a fold similar to the staphylococcal pore-forming toxins, but in VCC an amino-terminal pro-domain and two carboxy-terminal lectin domains decorate the cytolytic domain. The pro-domain masks a protomer surface that likely participates in inter-protomer interactions in the cytolytic oligomer, thereby explaining why proteolytic cleavage and movement of the pro-domain is necessary for toxin activation. A single beta-octyl glucoside molecule outlines a possible receptor binding site on one lectin domain, and removal of this domain leads to a tenfold decrease in lytic activity toward rabbit erythrocytes. VCC activated by proteolytic cleavage assembles into an oligomeric species upon addition of soybean asolectin/cholesterol liposomes and this oligomer was purified in detergent micelles. Analytical ultracentrifugation and crystallographic analysis indicate that the resulting VCC oligomer is a heptamer. Taken together, these studies define the architecture of a pore forming toxin and associated lectin domains, confirm the stoichiometry of the assembled oligomer as heptameric, and suggest a common mechanism of assembly for staphylococcal and Vibrio cytolytic toxins.
About this Structure
1XEZ is a Protein complex structure of sequences from Vibrio cholerae with as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structure of the Vibrio cholerae cytolysin (VCC) pro-toxin and its assembly into a heptameric transmembrane pore., Olson R, Gouaux E, J Mol Biol. 2005 Jul 29;350(5):997-1016. PMID:15978620
Page seeded by OCA on Thu Feb 21 15:54:03 2008
