Document Detail


Electrospray mass spectrometry of NeuAc oligomers associated with the C fragment of the tetanus toxin.
MedLine Citation:
PMID:  16713287     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The Clostridial neurotoxins, botulinum and tetanus, gain entry into motor neurons by binding to the sialic or N-acetylneuraminic acid (NeuAc) residues of gangliosides and specific protein receptors attached to the cell's surface. While the C-fragment of tetanus toxin (TetC) has been identified to be the ganglioside binding domain, remarkably little is known about how this domain discriminates between the structural features of different gangliosides. We have used electrospray ionization mass spectrometry (ESI-MS) to examine the formation of complexes between TetC and carbohydrates containing NeuAc groups to determine how NeuAc residues contribute to ganglioside binding. ESI-MS was used to obtain an estimate of the dissociation constants (KD values) for TetC binding to a number of related NeuAc-containing carbohydrates (sialyllactose and disialyllactose), as well as six (NeuAc)n oligomers (n = 1-6). KD values were found to range between approximately 10-35 microM. The strength of the interactions between the C fragment and (NeuAc)n are consistent with the topography of the targeting domain of tetanus toxin and the nature of its carbohydrate binding sites. These results suggest that the targeting domain of tetanus toxin contains two binding sites that can accommodate NeuAc (or a dimer) and that NeuAc may play an important role in ganglioside binding and molecular recognition, a process critical for normal cell function and one frequently exploited by toxins, bacteria, and viruses to facilitate their entrance into cells.
Authors:
Maria C Prieto Conway; Randy M Whittal; Michael A Baldwin; A L Burlingame; Rod Balhorn
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2006-05-19
Journal Detail:
Title:  Journal of the American Society for Mass Spectrometry     Volume:  17     ISSN:  1044-0305     ISO Abbreviation:  J. Am. Soc. Mass Spectrom.     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-07-03     Completed Date:  2007-07-03     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  9010412     Medline TA:  J Am Soc Mass Spectrom     Country:  United States    
Other Details:
Languages:  eng     Pagination:  967-76     Citation Subset:  IM    
Affiliation:
Chemistry and Materials Science Directorate, Lawrence Livermore National Laboratory, Livermore, California 94550, USA.
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MeSH Terms
Descriptor/Qualifier:
Binding Sites
Computer Simulation
Dimerization
Gangliosides / chemistry*
Models, Chemical*
N-Acetylneuraminic Acid / chemistry*
Peptide Fragments / chemistry*
Spectrometry, Mass, Electrospray Ionization / methods*
Tetanus Toxin / chemistry*
Grant Support
ID/Acronym/Agency:
RR01614/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Gangliosides; 0/Peptide Fragments; 0/Tetanus Toxin; 0/tetanus toxin fragment C; 131-48-6/N-Acetylneuraminic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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