Cryo-EM structure of the botulinum neurotoxin A/SV2B complex and its implications for translocation.

Botulinum neurotoxin A1 (BoNT/A1) belongs to the most potent toxins and is used as a major therapeutic agent. Neurotoxin conformation is crucial for its translocation to the neuronal cytosol, a key process for intoxication that is only poorly understood. To gain molecular insights into the steps preceding toxin translocation, we determine cryo-EM structures of BoNT/A1 alone and in complex with its receptor synaptic vesicle glycoprotein 2B (SV2B).

Identifying Selectivity Filters in Protein Biosensor for Ligand Screening.

Specialized sensing mechanisms in bacteria enable the identification of cognate ligands with remarkable selectivity in highly xenobiotic-polluted environments where these ligands are utilized as energy sources. Here, via integrating all-atom computer simulation, biochemical assay, and isothermal titration calorimetry measurements, we determine the molecular basis of MopR, a phenol biosensor's complex selection process of ligand entry. Our results reveal a set of strategically placed selectivity filters along the ligand entry pathway of MopR.