6ojp | pdb_00006ojp

Structure of glycolipid alpha-GSA[8,6P] in complex with mouse CD1d

spinqualitylabelsall models 6ojp, resolution 2.17Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ojp is a 2 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 7LP, BMA, FUC, GOL, MAN, NAG, PLM, SO4 Gene: Cd1d1, mCG_3074 (LK3 transgenic mice), B2m (LK3 transgenic mice) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [B2MG_MOUSE] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. Publication Abstract from PubMed Type I Natural Killer T (NKT) cells are a population of innate like T lymphocytes that rapidly respond to alpha-GalCer presented by CD1d, via the production of both pro and anti-inflammatory cytokines. While developing novel alpha-GalCer analogs that were meant to be utilized as potential adjuvants due to their production of pro-inflammatory cytokines (Th1 skewers), we generated alpha-galactosylsphingamides (alpha-GSA). Surprisingly, alpha-GSAs are not potent antigens in vivodespite their strong T-cell receptor (TCR)-binding affinities. Here, using surface plasmon resonance (SPR), antigen presentation assays, and X-ray crystallography (yielding crystal structures of 19 different binary [CD1d-glycolipid] or ternary [CD1d-glycolipid-TCR] complexes at resolutions between 1.67 and 2.85 A), we characterized the biochemical and structural details of alpha-GSA recognition by murine NKT cells. We identified a molecular switch within murine (m)CD1d that modulates NKT cell activation by alpha-GSAs. We found that the molecular switch involves a hydrogen bond interaction between Tyr-73 of mCD1d and the amide group oxygen of alpha-GSAs. We further established that the length of the acyl chain controls the positioning of the amide group with respect to the molecular switch and works synergistically with Tyr-73 to control NKT cell activity. In conclusion, our findings reveal important mechanistic insights into the presentation and recognition of glycolipids with polar moieties in an otherwise apolar milieu.These observations may inform the development alpha-GSAs as specific NKT cell antagonists to modulate immune responses. A molecular switch in mouse CD1d modulates natural killer T cell activation by alpha-galactosylsphingamides.,Wang J, Guillaume J, Janssens J, Remesh SG, Ying G, Bitra A, Van Calenbergh S, Zajonc DM J Biol Chem. 2019 Aug 7. pii: RA119.009963. doi: 10.1074/jbc.RA119.009963. PMID:31391251 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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