Structural Analysis of Botulinum Neurotoxins Type B and E by Cryo-EM

Kosenina, Sara (author): Stockholm University,Stockholms universitet,Institutionen för biokemi och biofysik

Martínez-Carranza, Markel (author): Stockholm University,Stockholms universitet,Institutionen för biokemi och biofysik

Davies, Jonathan R. (author): Stockholm University,Stockholms universitet,Institutionen för biokemi och biofysik

Masuyer, Geoffrey (author): Stockholm University,Stockholms universitet,Institutionen för biokemi och biofysik,University of Bath, UK

Stenmark, Pål (author): Stockholm University,Lunds universitet,Stockholms universitet,Institutionen för biokemi och biofysik,Lund University, Sweden,Strukturell biokemi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Structural Biochemistry,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments

(creator_code:org_t)

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Abstract Subject headings

Botulinum neurotoxins (BoNTs) are the causative agents of a potentially lethal paralytic disease targeting cholinergic nerve terminals. Multiple BoNT serotypes exist, with types A, B and E being the main cause of human botulism. Their extreme toxicity has been exploited for cosmetic and therapeutic uses to treat a wide range of neuromuscular disorders. Although naturally occurring BoNT types share a common end effect, their activity varies significantly based on the neuronal cell-surface receptors and intracellular SNARE substrates they target. These properties are the result of structural variations that have traditionally been studied using biophysical methods such as X-ray crystallography. Here, we determined the first structures of botulinum neurotoxins using single-particle cryogenic electron microscopy. The maps obtained at 3.6 and 3.7 Å for BoNT/B and /E, respectively, highlight the subtle structural dynamism between domains, and of the binding domain in particular. This study demonstrates how the recent advances made in the field of single-particle electron microscopy can be applied to bacterial toxins of clinical relevance and the botulinum neurotoxin family in particular.

NATURVETENSKAP -- Kemi (hsv//swe)
NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

By the author/editor: Kosenina, Sara; Martínez-Carranz ...; Davies, Jonathan ...; Masuyer, Geoffre ...; Stenmark, Pål

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biochemistry and ...

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