Structural analysis of the interaction between Shiga toxin B subunits and linear polymers bearing clustered globotriose residues.
We previously developed linear polymers bearing clustered trisaccharides of globotriaosylceramide (Gb3) as orally applicable Shiga toxin (Stx) neutralizers. Here, using a Gb3 polymer with a short spacer tethering the trisaccharide to the core, we found that shortening the spacer length markedly reduced the binding affinity for Stx2 but not Stx1. Moreover, mutational analysis revealed that the essential binding sites of the terminal trisaccharides were completely different between Stx1 and Stx2. These results provide the molecular basis for the interaction between Stx B subunits and Gb3 polymers.
Watanabe
Miho
M
Department of Clinical Pharmacology, Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.
Igai
Katsura
K
Matsuoka
Koji
K
Miyagawa
Atsushi
A
Watanabe
Toshiyuki
T
Yanoshita
Ryohei
R
Samejima
Yuji
Y
Terunuma
Daiyo
D
Natori
Yasuhiro
Y
Nishikawa
Kiyotaka
K
D020106:Acrylamide / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D002522:Chlorocebus aethiops; D019453:Escherichia coli O157 / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D022622:Shiga Toxin 1 / Q000737:chemistry* / Q000378:metabolism; D022641:Shiga Toxin 2 / Q000737:chemistry* / Q000378:metabolism; D014312:Trisaccharides / Q000737:chemistry* / Q000627:therapeutic use; D014709:Vero Cells
D011108:Polymers; D021122:Protein Subunits; D022622:Shiga Toxin 1; D022641:Shiga Toxin 2; D014312:Trisaccharides; D020106:Acrylamide; C113460:globotriose