The Structure of the Neurotoxin-associated Protein HA33/A from Clostridium botulinum Suggests a Reoccurring b-Trefoil Fold in the Progenitor Toxin Complex

0022-2836/$ see front matter q 2004 E Present address: J. Gu, San Diego Center, University of California San Drive, La Jolla, CA 92093, USA. Abbreviations used: HA, hemagg non-toxic non-hemagglutinin; BoNT neurotoxin; NAP, neurotoxin-associ root-mean-square deviation; TeNT, E-mail address of the correspond [email protected] The hemagglutinating protein HA33 from Clostridium botulinum is associated with the large botulinum neurotoxin secreted complexes and is critical in toxin protection, internalization, and possibly activation. We report the crystal structure of serotype A HA33 (HA33/A) at 1.5 Å resolution that contains a unique domain organization and a carbohydrate recognition site. In addition, sequence alignments of the other toxin complex components, including the neurotoxin BoNT/A, hemagglutinating protein HA17/A, and non-toxic non-hemagglutinating protein NTNHA/A, suggests that most of the toxin complex consists of a reoccurring b-trefoil fold. q 2004 Elsevier Ltd. All rights reserved.