8GLH

Crystal Structure of Human CD1b in Complex with Endogenous PC C40:5

Summary for 8GLH

• Entry DOI: 10.2210/pdb8glh/pdb
• Descriptor: T-cell surface glycoprotein CD1b, Beta-2-microglobulin, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-3)][alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (10 entities in total)
• Functional Keywords: antigen presentation, lipid, cd1b, phospholipid, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 49358.69

Authors

Farquhar, R.,Rossjohn, J.,Shahine, A. (deposition date: 2023-03-22, release date: 2023-09-20, Last modification date: 2024-11-06)

Primary citation

Huang, S.,Shahine, A.,Cheng, T.Y.,Chen, Y.L.,Ng, S.W.,Balaji, G.R.,Farquhar, R.,Gras, S.,Hardman, C.S.,Altman, J.D.,Tahiri, N.,Minnaard, A.J.,Ogg, G.S.,Mayfield, J.A.,Rossjohn, J.,Moody, D.B.
CD1 lipidomes reveal lipid-binding motifs and size-based antigen-display mechanisms.
Cell, 186:4583-4596.e13, 2023

PubMed Abstract: The CD1 system binds lipid antigens for display to T cells. Here, we solved lipidomes for the four human CD1 antigen-presenting molecules, providing a map of self-lipid display. Answering a basic question, the detection of >2,000 CD1-lipid complexes demonstrates broad presentation of self-sphingolipids and phospholipids. Whereas peptide antigens are chemically processed, many lipids are presented in an unaltered form. However, each type of CD1 protein differentially edits the self-lipidome to show distinct capture motifs based on lipid length and chemical composition, suggesting general antigen display mechanisms. For CD1a and CD1d, lipid size matches the CD1 cleft volume. CD1c cleft size is more variable, and CD1b is the outlier, where ligands and clefts show an extreme size mismatch that is explained by uniformly seating two small lipids in one cleft. Furthermore, the list of compounds that comprise the integrated CD1 lipidome supports the ongoing discovery of lipid blockers and antigens for T cells.

PubMed: 37725977
DOI: 10.1016/j.cell.2023.08.022

Experimental method

X-RAY DIFFRACTION (1.83 Å)