Differential role of molten globule and protein folding in distinguishing unique features of botulinum neurotoxin
Language: 
English
Abstract: 

Botulinum neurotoxins (BoNTs) are proteins of great interest not only because of their extreme toxicity but also paradoxically for their therapeutic applications. All the known serotypes (A-G) have varying degrees of longevity and potency inside the neuronal cell. Differential chemical modifications such as phosphorylation and ubiquitination have been suggested as possible mechanisms for their longevity, but the molecular basis of the longevity remains unclear. Since the endopeptidase domain (light chain; LC) of toxin apparently survives inside the neuronal cells for months, it is important to examine the structural features of this domain to understand its resistance to intracellular degradation. Published crystal structures (both botulinum neurotoxins and endopeptidase domain) have not provided adequate explanation for the intracellular longevity of the domain. Structural features obtained from spectroscopic analysis of LCA and LCB were similar, and a PRIME (PReImminent Molten Globule Enzyme) conformation appears to be responsible for their optimal enzymatic activity at 37∞C. LCE, on the other hand, was although optimally active at 37∞C, but its active conformation differed from the PRIME conformation of LCA and LCB. This study establishes and confirms our earlier finding that an optimally active conformation of these proteins in the form of PRIME exists for the most poisonous poison, botulinum neurotoxin. There are substantial variations in the structural and functional characteristics of these active molten globule related structures among the three BoNT endopeptidases examined. These differential conformations of LCs are important in understanding the fundamental structural features of proteins, and their possible connection to intracellular longevity could provide significant clues for devising new countermeasures and effective therapeutics.

Author(s): 
Kumar, Raj
Kukreja, Roshan V.
Cai, Shuowei
Singh, Bal R.
Item Type: 
Journal Article
Publication Title: 
Biochimica Et Biophysica Acta
Journal Abbreviation: 
Biochim. Biophys. Acta
Publication Date: 
2014-06
Publication Year: 
2014
Pages: 
1145-1152
Volume: 
1844
Issue: 
6
ISSN: 
0006-3002
DOI: 
10.1016/j.bbapap.2014.02.012
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 24568862

Turabian/Chicago Citation

Raj Kumar, Roshan V. Kukreja, Shuowei Cai and Bal R. Singh. 2014-06. "Differential role of molten globule and protein folding in distinguishing unique features of botulinum neurotoxin." Biochimica Et Biophysica Acta 1844: 6: 1145-1152. 10.1016/j.bbapap.2014.02.012.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1016/j.bbapap.2014.02.012 | issn = 0006-3002 | volume = 1844 | pages = 1145-1152 | last = Kumar | first = Raj | coauthors = Kukreja, Roshan V., Cai, Shuowei, Singh, Bal R. | title = Differential role of molten globule and protein folding in distinguishing unique features of botulinum neurotoxin | journal = Biochimica Et Biophysica Acta | date = 2014-06 | pmid = | pmc = }} </ref>