9OHU

CD1c presenting GM3 ganglioside

This is a non-PDB format compatible entry.

Summary for 9OHU

• Entry DOI: 10.2210/pdb9ohu/pdb
• Descriptor: T-cell surface glycoprotein CD1c/T-cell surface glycoprotein CD1b chimeric protein, Beta-2-microglobulin, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: cd1c, lipid mediated immunity, lipid antigen presentation, gm3, ganglioside, lipid binding protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 45708.22

Authors

Cao, T.P.,Rossjohn, J.,Shahine, A. (deposition date: 2025-05-05, release date: 2025-11-19, Last modification date: 2026-01-14)

Primary citation

Cao, T.P.,Liao, G.R.,Cheng, T.Y.,Chen, Y.,Ciacchi, L.,Fulford, T.S.,Farquhar, R.,Kollmorgen, J.,Mayfield, J.A.,Uldrich, A.P.,Ng, E.Z.Q.,Ogg, G.S.,Godfrey, D.I.,Gherardin, N.A.,Chen, Y.L.,Moody, D.B.,Shahine, A.,Rossjohn, J.
Sideways lipid presentation by the antigen-presenting molecule CD1c.
Nat Commun, 2025

PubMed Abstract: For the MHC, MR1 and CD1 systems, antigen recognition involves contact of the membrane distal surfaces of both the αβ T cell receptor (TCR) and the antigen-presenting molecule. Whether other antigen display mechanisms by antigen-presenting molecules operate remains unknown. Here, we report mass spectrometry analyses of endogenous lipids captured by CD1c when bound to an autoreactive αβ TCR. CD1c binds twenty-six lipid species with bulky headgroups that cannot fit within the tight TCR-CD1c interface. We determined the crystal structures of CD1c presenting several gangliosides, revealing a general mechanism whereby two lipids, rather than one, are bound in the CD1c cleft. Bulky lipids are oriented sideways so that their polar headgroups protrude laterally through a side portal of the CD1c molecule - an evolutionarily conserved structural feature. The sideways-presented ganglioside headgroups do not hinder TCR binding and so represent a mechanism that allows autoreactive TCR recognition of CD1c. In addition, ex vivo studies showed that the sideways-presented gangliosides can also represent TCR recognition determinants. These findings reveal that CD1c simultaneously presents two lipid antigens from the top and side of its cleft, a general mechanism that differs markedly from other antigen-presenting molecules.

PubMed: 41476042
DOI: 10.1038/s41467-025-67732-2

Experimental method

X-RAY DIFFRACTION (2.9 Å)