Structure‐based sequence alignment for the β‐trefoil subdomain of the clostridial neurotoxin family provides residue level information about the putative ganglioside binding site

FEBS Letters

Venclovas, C̆eslovas²  Ginalski, Krzysztof²  Lesyng, Bogdan¹  Fidelis, Krzysztof² 

[1] Department of Biophysics, Institute of Experimental Physics, University of Warsaw, Żwirki i Wigury 93, 02-089 Warsaw, Poland;Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, CA 94551, USA

关键词: Tetanus neurotoxin;    Botulinum neurotoxin;    β-trefoil;    Sequence alignment;    Homology modeling;    Ganglioside binding site;   

DOI  :  10.1016/S0014-5793(00)01954-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Clostridial neurotoxins embrace a family of extremely potent toxins comprised of tetanus toxin (TeNT) and seven different serotypes of botulinum toxin (BoNT/A–G). The β-trefoil subdomain of the C-terminal part of the heavy chain (H_C), responsible for ganglioside binding, is the most divergent region in clostridial neurotoxins with sequence identity as low as 15%. We re-examined the alignment between family sequences within this subdomain, since in this region all alignments published to date show obvious inconsistencies with the β-trefoil fold. The final alignment was obtained by considering the general constraints imposed by this fold, and homology modeling studies based on the TeNT structure. Recently solved structures of BoNT/A confirm the validity of this structure-based approach. Taking into account biochemical data and crystal structures of TeNT and BoNT/A, we also re-examined the location of the putative ganglioside binding site and, using the new alignment, characterized this site in other BoNT serotypes.

【 授权许可】

Unknown