Deubiquitinating enzyme VCIP135 dictates the duration of botulinum neurotoxin type A intoxication
Abstract
Botulinum neurotoxins (BoNTs) are the most potent biological toxins. These proteases function by cleaving SNARE proteins, leading to paralysis and death from respiratory failure. BoNT serotype A (BoNT/A) has the most prolonged symptoms due to an extraordinarily stable catalytic light chain (LCA). BoNT/A intoxication can occur through ingestion (either sporadically or from a common food source), as a consequence of a clinical mishap, or potentially through bioterrorism, which would require mass mechanical ventilation. We report that LCA persistence is due to a particular deubiquitinating enzyme that binds a specific region of LCA and prevents its ubiquitin-dependent proteasomal degradation. These findings represent an essential step toward developing targeted molecular approaches to reducing morbidity and mortality from this toxin.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 05, 2017
- Source ID
- 10.1073/pnas.1621076114
Entities
People
- Allan M. Weissman
- Archana Kotiya
- Erkan Kiris
- George A. Oyler
- Lino Tessarollo
- Mei Yang
- Sina Bavari
- Yien Che Tsai
Organizations
- Defense Threat Reduction Agency
- Johns Hopkins University
- National Cancer Institute
- National Institute of Allergy and Infectious Diseases
- United States Army Medical Research Institute of Infectious Diseases