title: Sugar-induced conformational change found in the HA-33/HA-17 trimer of the botulinum toxin complex.
abstract: Large-sized botulinum toxin complex (L-TC) is formed by conjugation of neurotoxin, nontoxic nonhemagglutinin and hemagglutinin (HA) complex. The HA complex is formed by association of three HA-70 molecules and three HA-33/HA-17 trimers, comprised of a single HA-17 and two HA-33 proteins. The HA-33/HA-17 trimer isolated from serotype D L-TC has the ability to bind to and penetrate through the intestinal epithelial cell monolayer in a sialic acid-dependent manner, and thus it plays an important role in toxin delivery through the intestinal cell wall. In this study, we determined the solution structure of the HA-33/HA-17 trimer by using small-angle X-ray scattering (SAXS). The SAXS image of HA-33/HA-17 exhibited broadly similar appearance to the crystal image of the complex. On the other hand, in the presence of N-acetylneuraminic acid, glucose and galactose, the solution structure of the HA-33/HA-17 trimer was drastically altered compared to the structure in the absence of the sugars. Sugar-induced structural change of the HA-33/HA-17 trimer may contribute to cell binding and subsequent transport across the intestinal cell layer.
authors.affiliation: Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri, Hokkaido 099-2493, Japan. y3sagane@bioindustry.nodai.ac.jp
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Sagane
authors.forename: Shintaro
authors.initials: S
authors.lastname: Hayashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Miyashita
authors.forename: Ken
authors.initials: K
authors.lastname: Inui
authors.forename: Keita
authors.initials: K
authors.lastname: Miyata
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yajima
authors.forename: Tomonori
authors.initials: T
authors.lastname: Suzuki
authors.forename: Kimiko
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Akihito
authors.initials: A
authors.lastname: Yamano
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nishikawa
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohyama
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Watanabe
authors.forename: Koichi
authors.initials: K
authors.lastname: Niwa
mesh_terms: D001905:Botulinum Toxins / Q000737:chemistry*; D005690:Galactose / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006388:Hemagglutinins / Q000737:chemistry; D008958:Models, Molecular; D019158:N-Acetylneuraminic Acid / Q000494:pharmacology; D011487:Protein Conformation / Q000187:drug effects*; D055503:Protein Multimerization / Q000187:drug effects*; D053838:Scattering, Small Angle; D014961:X-Ray Diffraction
chemical_list: D006388:Hemagglutinins; C118973:hemagglutinin 33 protein, Clostridium botulinum; D001905:Botulinum Toxins; D019158:N-Acetylneuraminic Acid; D005947:Glucose; D005690:Galactose
keywords: Clostridium botulinum; Hemagglutinin; Small-angle X-ray scattering; Structural dynamics; Toxin complex