Discovery of a new sialic acid binding region that regulates Siglec-7

Nao Yamakawa, Yu Yasuda, Atsushi Yoshimura, Ami Goshima, Paul R. Crocker, Gérard Vergoten, Yuji Nishiura, Takashi Takahashi, Shinya Hanashima, Kana Matsumoto, Yoshiki Yamaguchi, Hiroshi Tanaka, Ken Kitajima, Chihiro Sato (Lead / Corresponding author)

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Abstract

Siglec-7 is a human CD33-like siglec, and is localised predominantly on human natural killer (NK) cells and monocytes. Siglec-7 is considered to function as an immunoreceptor in a sialic acid-dependent manner. However, the underlying mechanisms linking sialic acid-binding and function remain unknown. Here, to gain new insights into the ligand-binding properties of Siglec-7, we carried out in silico analysis and site-directed mutagenesis, and found a new sialic acid-binding region (site 2 containing R67) in addition to the well-known primary ligand-binding region (site 1 containing R124). This was supported by equilibrium dialysis, STD-NMR experiments, and inhibition analysis of GD3-binding toward Siglec-7 using synthetic sialoglycoconjugates and a comprehensive set of ganglioside-based glycoconjugates. Our results suggest that the two ligand-binding sites are potentially controlled by each other due to the flexible conformation of the C-C' loop of Siglec-7.

Original languageEnglish
Article number8647
Pages (from-to)1-14
Number of pages14
JournalScientific Reports
Volume10
Issue number1
Early online date26 May 2020
DOIs
Publication statusPublished - 26 May 2020

Keywords

  • Glycobiology
  • Glycoconjugates

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    Yamakawa, N., Yasuda, Y., Yoshimura, A., Goshima, A., Crocker, P. R., Vergoten, G., Nishiura, Y., Takahashi, T., Hanashima, S., Matsumoto, K., Yamaguchi, Y., Tanaka, H., Kitajima, K., & Sato, C. (2020). Discovery of a new sialic acid binding region that regulates Siglec-7. Scientific Reports, 10(1), 1-14. [8647]. https://doi.org/10.1038/s41598-020-64887-4