Building-block architecture of botulinum toxin complex: Conformational changes provide insights into the hemagglutination ability of the complex
| Autor: | Akihito Yamano, Yoshimasa Sagane, Takashi Matsumoto, Kimiko Hasegawa, Koichi Niwa, Toshihiro Watanabe, Tomonori Suzuki |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Hemagglutination Biophysics Trimer BoNT botulinum neurotoxin medicine.disease_cause Biochemistry DAM dummy atom model TC toxin complex lcsh:Biochemistry 03 medical and health sciences medicine lcsh:QD415-436 TEM transmission electron microscopy Polyacrylamide gel electrophoresis lcsh:QH301-705.5 NTNHA nontoxic nonhemagglutinin Small-angle X-ray scattering Chemistry SAXS small-angle X-ray scattering QCM quartz crystal microbalance Botulinum toxin Solution structure Botulinum neurotoxin Crystallography 030104 developmental biology lcsh:Biology (General) SDS-PAGE sodium dodecyl sulfate polyacrylamide gel electrophoresis Clostridium botulinum medicine.drug Research Article HA hemagglutinin |
| Zdroj: | Biochemistry and Biophysics Reports, Vol 9, Iss C, Pp 67-71 (2017) Biochemistry and Biophysics Reports |
| ISSN: | 2405-5808 |
| Popis: | Clostridium botulinum produces the botulinum neurotoxin (BoNT). Previously, we provided evidence for the “building-block” model of botulinum toxin complex (TC). In this model, a single BoNT is associated with a single nontoxic nonhemagglutinin (NTNHA), yielding M-TC; three HA-70 molecules are attached and form M-TC/HA-70, and one to three “arms” of the HA-33/HA-17 trimer (two HA-33 and one HA-17) further bind to M-TC/HA-70 via HA-17 and HA-70 binding, yielding one-, two-, and three-arm L-TC. Of all TCs, only the three-arm L-TC caused hemagglutination. In this study, we determined the solution structures for the botulinum TCs using small-angle X-ray scattering (SAXS). The mature three-arm L-TC exhibited the shape of a “bird spreading its wings”, in contrast to the model having three “arms”, as revealed by transmission electron microscopy. SAXS images indicated that one of the three arms of the HA-33/HA-17 trimer bound to both HA-70 and BoNT. Taken together, these findings regarding the conformational changes in the building-block architecture of TC may explain why only three-arm L-TC exhibited hemagglutination. Highlights • We examined the structures of botulinum TCs using SAXS. • The mature three-arm L-TC exhibited the shape of a “bird spreading its wings”. • One of the three arms of the HA-33/HA-17 trimer bound to both HA-70 and BoNT. • The building-block architecture may explain hemagglutination by the three-arm L-TC. |
| Databáze: | OpenAIRE |
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