A versatile soluble siglec scaffold for sensitive and quantitative detection of glycan ligands

Emily Rodrigues, Jaesoo Jung, Heajin Park, Caleb Loo, Sepideh Soukhtehzari, Elena N. Kitova, Fahima Mozaneh, Gour Daskhan, Edward N. Schmidt, Vivian Aghanya, Susmita Sarkar, Laura Streith, Chris D. Laurent, Linh Nguyen, Jean-Philippe Julien, Lori J. West, Karla C. Williams, John S. Klassen and Matthew S. Macauley ()
Additional contact information
Emily Rodrigues: University of Alberta
Jaesoo Jung: University of Alberta
Heajin Park: University of Alberta
Caleb Loo: University of Alberta
Sepideh Soukhtehzari: University of British Columbia
Elena N. Kitova: University of Alberta
Fahima Mozaneh: University of Alberta
Gour Daskhan: University of Alberta
Edward N. Schmidt: University of Alberta
Vivian Aghanya: University of Alberta
Susmita Sarkar: University of Alberta
Laura Streith: University of Alberta
Chris D. Laurent: University of Alberta
Linh Nguyen: University of Alberta
Jean-Philippe Julien: University of Toronto
Lori J. West: University of Alberta
Karla C. Williams: University of British Columbia
John S. Klassen: University of Alberta
Matthew S. Macauley: University of Alberta

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract Sialic acid-binding immunoglobulin-type lectins (Siglecs) are immunomodulatory receptors that are regulated by their glycan ligands. The connections between Siglecs and human disease motivate improved methods to detect Siglec ligands. Here, we describe a new versatile set of Siglec-Fc proteins for glycan ligand detection. Enhanced sensitivity and selectivity are enabled through multimerization and avoiding Fc receptors, respectively. Using these Siglec-Fc proteins, Siglec ligands are systematically profiled on healthy and cancerous cells and tissues, revealing many unique patterns. Additional features enable the production of small, homogenous Siglec fragments and development of a quantitative ligand-binding mass spectrometry assay. Using this assay, the ligand specificities of several Siglecs are clarified. For CD33 (Siglec-3), we demonstrate that it recognizes both α2-3 and α2-6 sialosides in solution and on cells, which has implications for its link to Alzheimer’s disease susceptibility. These soluble Siglecs reveal the abundance of their glycan ligands on host cells as self-associated molecular patterns.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18907-6

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DOI: 10.1038/s41467-020-18907-6

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