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Unveiling Molecular Recognition of Sialoglycans by Human Siglec-10

31 Pages Posted: 13 May 2020 Publication Status: Published

See all articles by Rosa Ester Forgione

Rosa Ester Forgione

- Dipartimento di Scienze Chimiche

C. Di Carluccio

- Dipartimento di Scienze Chimiche

Juan Guzmán-Caldentey

CIB-CSIC - Department of Structural & Chemical Biology

Rosa Gaglione

- Dipartimento di Scienze Chimiche

Filomena Battista

- Dipartimento di Scienze Chimiche

Fabrizio Chiodo

Vrije Universiteit Amsterdam - Amsterdam Infection and Immunity Institute

Yoshiyuki Manabe

Osaka University - Department of Chemistry

Angela Arciello

- Dipartimento di Scienze Chimiche

Pompea Del Vecchio

- Dipartimento di Scienze Chimiche

Koichi Fukase

Osaka University - Department of Chemistry

Antonio Molinaro

- Dipartimento di Scienze Chimiche

Sonsoles Martín-Santamaría

CIB-CSIC - Department of Structural & Chemical Biology

Paul R. Crocker Crocker

University of Dundee - Division of Cell Signalling and Immunology

Roberta Marchetti

- Dipartimento di Scienze Chimiche

Alba Silipo

- Dipartimento di Scienze Chimiche

More...

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. Though, a detailed understanding of sialoglycans recognition by Siglec-10 is still an unmet challenge; neither the crystal structure of the protein nor the atomic description of its interactions with complex glycans had been indeed previously described.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’ interactome and conformation upon binding, and to afford a description of the 3D complexes. Our outcomes provide a privileged structural perspective for the rational design and development of novel high affinity ligands to control the receptor functionality.

Keywords: Siglecs, molecular recognition, N-glycans, NMR

Suggested Citation

Forgione, Rosa Ester and Di Carluccio, C. and Guzmán-Caldentey, Juan and Gaglione, Rosa and Battista, Filomena and Chiodo, Fabrizio and Manabe, Yoshiyuki and Arciello, Angela and Del Vecchio, Pompea and Fukase, Koichi and Molinaro, Antonio and Martín-Santamaría, Sonsoles and Crocker, Paul R. Crocker and Marchetti, Roberta and Silipo, Alba, Unveiling Molecular Recognition of Sialoglycans by Human Siglec-10. Available at SSRN: https://ssrn.com/abstract=3587003 or http://dx.doi.org/10.2139/ssrn.3587003
This version of the paper has not been formally peer reviewed.

Rosa Ester Forgione

- Dipartimento di Scienze Chimiche

Italy

C. Di Carluccio

- Dipartimento di Scienze Chimiche

Italy

Juan Guzmán-Caldentey

CIB-CSIC - Department of Structural & Chemical Biology

United States

Rosa Gaglione

- Dipartimento di Scienze Chimiche

Italy

Filomena Battista

- Dipartimento di Scienze Chimiche

Italy

Fabrizio Chiodo

Vrije Universiteit Amsterdam - Amsterdam Infection and Immunity Institute

United States

Yoshiyuki Manabe

Osaka University - Department of Chemistry

United States

Angela Arciello

- Dipartimento di Scienze Chimiche

Italy

Pompea Del Vecchio

- Dipartimento di Scienze Chimiche

Italy

Koichi Fukase

Osaka University - Department of Chemistry

United States

Antonio Molinaro

- Dipartimento di Scienze Chimiche

Italy

Sonsoles Martín-Santamaría

CIB-CSIC - Department of Structural & Chemical Biology

United States

Paul R. Crocker Crocker

University of Dundee - Division of Cell Signalling and Immunology

United States

Roberta Marchetti (Contact Author)

- Dipartimento di Scienze Chimiche

Italy

Alba Silipo

- Dipartimento di Scienze Chimiche ( email )

Italy

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