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.
Department of Clinical Pharmacology, Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.
Miho
M
Watanabe
Katsura
K
Igai
Koji
K
Matsuoka
Atsushi
A
Miyagawa
Toshiyuki
T
Watanabe
Ryohei
R
Yanoshita
Yuji
Y
Samejima
Daiyo
D
Terunuma
Yasuhiro
Y
Natori
Kiyotaka
K
Nishikawa
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