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Title: Molecular assembly of Clostridium botulinum progenitor M complex of type E

Clostridium botulinum neurotoxin (BoNT) is released as a progenitor complex, in association with a non-toxic-non-hemagglutinin protein (NTNH) and other associated proteins. We have determined the crystal structure of M type Progenitor complex of botulinum neurotoxin E [PTC-E(M)], a heterodimer of BoNT and NTNH. The crystal structure reveals that the complex exists as a tight, interlocked heterodimer of BoNT and NTNH. The crystal structure explains the mechanism of molecular assembly of the complex and reveals several acidic clusters at the interface responsible for association at low acidic pH and disassociation at basic/neutral pH. Furthermore, the similarity of the general architecture between the PTC-E(M) and the previously determined PTC-A(M) strongly suggests that the progenitor M complexes of all botulinum serotypes may have similar molecular arrangement, although the neurotoxins apparently can take very different conformation when they are released from the M complex.
 [1] ;  [1] ;  [2] ;  [3] ;  [1]
  1. Brookhaven National Lab. (BNL), Upton, NY (United States)
  2. Brookhaven National Lab. (BNL), Upton, NY (United States); Stony Brook Univ., Stony Brook, NY (United States)
  3. Institute of Advanced Sciences, Dartmouth, MA (United States)
Publication Date:
Report Number(s):
Journal ID: ISSN 2045-2322; 456140124
Grant/Contract Number:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 5; Journal Issue: 11; Journal ID: ISSN 2045-2322
Nature Publishing Group
Research Org:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org:
Defense Threat Reduction Agency (DTRA)
Country of Publication:
United States
59 BASIC BIOLOGICAL SCIENCES; Closttidium Botulinum; crystal structure; NTNH; biophysics; electron microscopy; structural biology; X-ray crystallography
OSTI Identifier: