Unveiling Molecular Recognition of Sialoglycans by Human Siglec-10

Rosa Ester Forgione, Cristina Di Carluccio, Juan Guzmán-Caldentey, Rosa Gaglione, Filomena Battista, Fabrizio Chiodo, Yoshiyuki Manabe, Angela Arciello, Pompea Del Vecchio, Koichi Fukase, Antonio Molinaro, Sonsoles Martín-Santamaría, Paul R. Crocker, Roberta Marchetti (Lead / Corresponding author), Alba Silipo (Lead / Corresponding author)

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Abstract

Siglec-10 is an inhibitory I-type lectin selectively recognizing sialoglycans exposed on cell surfaces, involved in several patho-physiological processes. The key role Siglec-10 plays in the regulation of immune cell functions has made it a potential target for the development of immunotherapeutics against a broad range of diseases. However, the crystal structure of the protein has not been resolved for the time being and the atomic description of Siglec-10 interactions with complex glycans has not been previously unraveled. We present here the first insights of the molecular mechanisms regulating the interaction between Siglec-10 and naturally occurring sialoglycans. We used combined spectroscopic, computational and biophysical approaches to dissect glycans’ epitope mapping and conformation upon binding in order to afford a description of the 3D complexes. Our outcomes provide a structural perspective for the rational design and development of high-affinity ligands to control the receptor functionality.
Original languageEnglish
Article number101231
Pages (from-to)1-29
Number of pages29
JournaliScience
Volume23
Issue number6
Early online date2 Jun 2020
DOIs
Publication statusPublished - 26 Jun 2020

Keywords

  • Biochemistry
  • Biochemistry Methods
  • Data Analysis in Structural Biology
  • Structural Biology

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    Forgione, R. E., Di Carluccio, C., Guzmán-Caldentey, J., Gaglione, R., Battista, F., Chiodo, F., Manabe, Y., Arciello, A., Del Vecchio, P., Fukase, K., Molinaro, A., Martín-Santamaría, S., Crocker, P. R., Marchetti, R., & Silipo, A. (2020). Unveiling Molecular Recognition of Sialoglycans by Human Siglec-10. iScience, 23(6), 1-29. [101231]. https://doi.org/10.1016/j.isci.2020.101231