9O6J

Structure of Siglec-10 in complex with 2,3-Sialyllactose

Summary for 9O6J

• Entry DOI: 10.2210/pdb9o6j/pdb
• Descriptor: Sialic acid-binding Ig-like lectin 10, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-galactopyranose-(1-4)-D-glucose, ... (5 entities in total)
• Functional Keywords: siglec, receptor, sialic acid, immune system
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 3
• Total formula weight: 75647.66

Authors

Medina, E.,Ming, Q.,Tran, T.H.,Luca, V.C. (deposition date: 2025-04-13, release date: 2026-02-25, Last modification date: 2026-09-09)

Primary citation

Medina, E.,Mason, C.,Tran, T.H.,Julia, E.P.,Ming, Q.,Taibi, L.M.,Hwu, P.,Maute, R.L.,Burg, J.S.,Luca, V.C.
Structural basis for sialoglycan recognition by the immune inhibitory receptor Siglec-10.
Structure, 34:768-777.e5, 2026

PubMed Abstract: Sialic acid-binding immunoglobulin-like lectin 10 (Siglec-10) inhibits immune cell function by sensing the presence of sialylated glycoproteins. Here, we determined structures of Siglec-10 bound to sialyllactose (SL) ligands to visualize the molecular recognition events underlying Siglec-10 signaling. The structures reveal that domain 1 (D1) of Siglec-10 engages SL using a non-conserved, selectivity determining CC' loop. Siglec-10 binds α2,3- and α2,6-linked SL with similar affinities despite minor additional contacts between D1 and the α2,3-SL galactose. Homodimerization of Siglec-10 is mediated by a hydrophobic domain 2 (D2) interface, and mutation of this interface ablates cellular binding similarly to mutations in the CC' loop and glycan-binding site. Surprisingly, knockout of the putative Siglec-10 ligand, CD24, did not affect binding to breast cancer cells, indicating that Siglec-10 has a broader-than-expected glycoprotein recognition profile. These findings emphasize how a complex interplay between Siglec-10 multimerization and ligand engagement facilitate cell surface interactions.

PubMed: 41747717
DOI: 10.1016/j.str.2026.01.018

Experimental method

X-RAY DIFFRACTION (3.39 Å)