4QD2
Molecular basis for disruption of E-cadherin adhesion by botulinum neurotoxin A complex
Summary for 4QD2
| Entry DOI | 10.2210/pdb4qd2/pdb |
| Descriptor | Hemagglutinin component HA33, Hemagglutinin component HA17, Hemagglutinin component HA70, ... (6 entities in total) |
| Functional Keywords | oral toxicity, botulinum neurotoxin, e-cadherin, ha70, ha17, ha33, cell adhesion |
| Biological source | Clostridium botulinum More |
| Cellular location | Cell junction: P09803 |
| Total number of polymer chains | 10 |
| Total formula weight | 274921.05 |
| Authors | Lee, K.,Zhong, X.,Gu, S.,Kruel, A.,Dorner, M.B.,Perry, K.,Rummel, A.,Dong, M.,Jin, R. (deposition date: 2014-05-13, release date: 2014-06-25, Last modification date: 2023-09-20) |
| Primary citation | Lee, K.,Zhong, X.,Gu, S.,Kruel, A.M.,Dorner, M.B.,Perry, K.,Rummel, A.,Dong, M.,Jin, R. Molecular basis for disruption of E-cadherin adhesion by botulinum neurotoxin A complex. Science, 344:1405-1410, 2014 Cited by PubMed Abstract: 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. PubMed: 24948737DOI: 10.1126/science.1253823 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
Download full validation report
