Structural studies of large clostridium toxins
EMSL Project ID
51271
Abstract
Bacterial toxins are virulence factors that manipulate host cell functions and cause a myriad of serious diseases. We propose two aims to study the structure and function of Clostridium difficile toxins (TcdA and TcdB) and Clostridium botulinum neurotoxins (BoNTs), respectively. (1) TcdA and especially TcdB cause C. diff infection (CDI). We propose to determine the structure of TcdB holotoxin in complex with its host cell receptors using CryoEM, which will establish the molecular basis for toxin-receptor recognition and advance mechanistic understanding of TcdB pathogenesis and therapy of CDI. (2) BoNTs are naturally produced in the form of progenitor toxin complexes (PTCs), which are large molecular weight multi-protein complexes. We propose to determine the structures of genetically inactivated nontoxic PTCs using CryoEM. These structures will reveal the molecular basis for PTC assembly, which will help us better understand the intoxication pathway of BoNTs and develop new therapies to treat disease botulism.
Project Details
Start Date
2020-02-15
End Date
2021-03-17
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members