4qd2

Molecular basis for disruption of E-cadherin adhesion by botulinum neurotoxin A complex

spinqualitylabelsall models 4qd2, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4qd2 is a 10 chain structure with sequence from Clostridium botulinum A str. Hall and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.4Å Ligands: CA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A5HZZ6_CLOBH Publication Abstract from PubMed How botulinum neurotoxins (BoNTs) cross the host intestinal epithelial barrier in foodborne botulism is poorly understood. Here, we present the crystal structure of a clostridial hemagglutinin (HA) complex of serotype BoNT/A bound to the cell adhesion protein E-cadherin at 2.4 angstroms. The HA complex recognizes E-cadherin with high specificity involving extensive intermolecular interactions and also binds to carbohydrates on the cell surface. Binding of the HA complex sequesters E-cadherin in the monomeric state, compromising the E-cadherin-mediated intercellular barrier and facilitating paracellular absorption of BoNT/A. We reconstituted the complete 14-subunit BoNT/A complex using recombinantly produced components and demonstrated that abolishing either E-cadherin- or carbohydrate-binding of the HA complex drastically reduces oral toxicity of BoNT/A complex in vivo. Together, these studies establish the molecular mechanism of how HAs contribute to the oral toxicity of BoNT/A. Molecular basis for disruption of E-cadherin adhesion by botulinum neurotoxin A complex.,Lee K, Zhong X, Gu S, Kruel AM, Dorner MB, Perry K, Rummel A, Dong M, Jin R Science. 2014 Jun 20;344(6190):1405-10. doi: 10.1126/science.1253823. PMID:24948737 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cadherin 3D structures Hemagglutinin 3D structures

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