3cqf

Crystal structure of anthrolysin O (ALO)

spinqualitylabelsall models 3cqf, resolution 3.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3cqf is a 2 chain structure with sequence from Bacillus anthracis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.1Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A6L7HHW7_BACAN A cholesterol-dependent toxin that causes cytolysis by forming pores in cholesterol containing host membranes. After binding to target membranes, the protein undergoes a major conformation change, leading to its insertion in the host membrane and formation of an oligomeric pore complex. Cholesterol is required for binding to host membranes, membrane insertion and pore formation; cholesterol binding is mediated by a Thr-Leu pair in the C-terminus. Can be reversibly inactivated by oxidation.[RuleBase:RU364025] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Anthrolysin O (ALO) is a pore-forming, cholesterol-dependent cytolysin (CDC) secreted by Bacillus anthracis, the etiologic agent for anthrax. Growing evidence suggests the involvement of ALO in anthrax pathogenesis. Here, we show that the apical application of ALO decreases the barrier function of human polarized epithelial cells as well as increases intracellular calcium and the internalization of the tight junction protein occludin. Using pharmacological agents, we also found that barrier function disruption requires increased intracellular calcium and protein degradation. We also report a crystal structure of the soluble state of ALO. Based on our analytical ultracentrifugation and light scattering studies, ALO exists as a monomer. Our ALO structure provides the molecular basis as to how ALO is locked in a monomeric state, in contrast to other CDCs that undergo antiparallel dimerization or higher order oligomerization in solution. ALO has four domains and is globally similar to perfringolysin O (PFO) and intermedilysin (ILY), yet the highly conserved undecapeptide region in domain 4 (D4) adopts a completely different conformation in all three CDCs. Consistent with the differences within D4 and at the D2-D4 interface, we found that ALO D4 plays a key role in affecting the barrier function of C2BBE cells, whereas PFO domain 4 cannot substitute for this role. Novel structural elements and unique cellular functions of ALO revealed by our studies provide new insight into the molecular basis for the diverse nature of the CDC family. Cellular functions and X-ray structure of anthrolysin O, a cholesterol-dependent cytolysin secreted by Bacillus anthracis.,Bourdeau RW, Malito E, Chenal A, Bishop BL, Musch MW, Villereal ML, Chang EB, Mosser EM, Rest RF, Tang WJ J Biol Chem. 2009 May 22;284(21):14645-56. Epub 2009 Mar 23. PMID:19307185 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cytolysin 3D structures

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