Ellen WalsePhD Student

Strucutrual studies of the Botulinum neurotoxins

The Botulinum neurotoxins (BoNTs) are the deadliest substances known. BoNTs are produced by the spore-forming anaerobic bacteria Clostridium botulinum and cause the disease botulism. The toxin targets the junction of motor neurons and muscles, blocking the release of the neurotransmitter acetylcholine and causing muscle paralysis. C. botulinum naturally exists in soil, river and sea water and have three main intoxication routes. Foodborne botulism from consuming improperly processed foods, wound botulism from toxin entry into an open wound, and infant botulism from Clostridium colonization in an infant’s gut. The structural features and presence of accessory proteins enable BoNTs to survive the gastrointestinal tract, enter the blood stream and reach neurons through receptor recognition. Historically, BoNTs have been divided into seven serotypes (A-G). In recent years BoNT-like toxins outside of the genus Clostridium have been identified, including BoNT/Wo, BoNT/En, PMP1, BoNT/Bt and Furfuritoxin. Despite their extreme toxicity, BoNT serotypes A and B are approved for treating neuromuscular disorders involving involuntarily muscle spasms or contractions, such as cerebral palsy. They are also used for chronic migraine treatment and cosmetic applications to reduce wrinkles and forehead frown lines. Structural studies using X-ray crystallography and single-particle cryo‑EM are important for understanding BoNT function and mechanism of action, with the goal to improve their therapeutic properties.