6cx9

From Proteopedia

Structure of alpha-GSA[16,6P] bound by CD1d and in complex with the Va14Vb8.2 TCR

Structural highlights

6cx9 is a 4 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.36Å
Ligands:	EM4, FUC, NA, NAG
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CD1D1_MOUSE Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells.^[1] ^[2] ^[3]

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations

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References

↑ Jayawardena-Wolf J, Benlagha K, Chiu YH, Mehr R, Bendelac A. CD1d endosomal trafficking is independently regulated by an intrinsic CD1d-encoded tyrosine motif and by the invariant chain. Immunity. 2001 Dec;15(6):897-908. PMID:11754812
↑ Zajonc DM, Maricic I, Wu D, Halder R, Roy K, Wong CH, Kumar V, Wilson IA. Structural basis for CD1d presentation of a sulfatide derived from myelin and its implications for autoimmunity. J Exp Med. 2005 Dec 5;202(11):1517-26. Epub 2005 Nov 28. PMID:16314439 doi:10.1084/jem.20051625
↑ Zajonc DM, Cantu C 3rd, Mattner J, Zhou D, Savage PB, Bendelac A, Wilson IA, Teyton L. Structure and function of a potent agonist for the semi-invariant natural killer T cell receptor. Nat Immunol. 2005 Aug;6(8):810-8. Epub 2005 Jul 10. PMID:16007091 doi:10.1038/ni1224
↑ Wang J, Guillaume J, Janssens J, Remesh SG, Ying G, Bitra A, Van Calenbergh S, Zajonc DM. A molecular switch in mouse CD1d modulates natural killer T cell activation by alpha-galactosylsphingamides. J Biol Chem. 2019 Aug 7. pii: RA119.009963. doi: 10.1074/jbc.RA119.009963. PMID:31391251 doi:http://dx.doi.org/10.1074/jbc.RA119.009963

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

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PDB ID 6cx9

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Categories: Large Structures | Mus musculus | Wang J | Zajonc D

6cx9

From Proteopedia

Structure of alpha-GSA[16,6P] bound by CD1d and in complex with the Va14Vb8.2 TCR

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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