FEBS Letters | |
Structure‐based sequence alignment for the β‐trefoil subdomain of the clostridial neurotoxin family provides residue level information about the putative ganglioside binding site | |
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 (HC), 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
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