PDBsum entry 6c6c

Immune system

PDB id: 6c6c

Contents

Protein chains

264 a.a.

98 a.a.

Ligands

NAG-NAG-BMA-MAN-MAN-FUC

NAG ×2

EMG

Metals

_NA ×2

Waters ×117

PDB id:

6c6c

Name:

Immune system

Title:

Structure of glycolipid agsa[20,6p] in complex with mouse cd1d

Structure:

Antigen-presenting glycoprotein cd1d1. Chain: a. Synonym: mcg3074,isoform cra_a. Engineered: yes. Beta-2-microglobulin. Chain: b. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: cd1d1, mcg_3074. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: b2m.

Resolution:

2.08Å R-factor: 0.201 R-free: 0.241

Authors:

D.M.Zajonc,J.Wang

Key ref:

J.Wang et al. (2019). A molecular switch in mouse CD1d modulates natural killer T cell activation by α-galactosylsphingamides. J Biol Chem, 294, 14345-14356. PubMed id: 31391251 DOI: 10.1074/jbc.RA119.009963

Date:

18-Jan-18 Release date: 30-Jan-19

Protein chain

P11609  (CD1D1_MOUSE) -  Antigen-presenting glycoprotein CD1d1 from Mus musculus

Seq: 336 a.a.

Struc: 264 a.a.

Protein chain

P01887  (B2MG_MOUSE) -  Beta-2-microglobulin from Mus musculus

Seq: 119 a.a.

Struc: 98 a.a.

DOI no: 10.1074/jbc.RA119.009963

J Biol Chem 294:14345-14356 (2019)

PubMed id: 31391251

A molecular switch in mouse CD1d modulates natural killer T cell activation by α-galactosylsphingamides.

J.Wang, J.Guillaume, J.Janssens, S.G.Remesh, G.Ying, A.Bitra, S.Van Calenbergh, D.M.Zajonc.

ABSTRACT

Type I natural killer T (NKT) cells are a population of innate like T lymphocytes that rapidly respond to α-GalCer presented by CD1d via the production of both pro- and anti-inflammatory cytokines. While developing novel α-GalCer analogs that were meant to be utilized as potential adjuvants because of their production of pro-inflammatory cytokines (Th1 skewers), we generated α-galactosylsphingamides (αGSA). Surprisingly, αGSAs are not potent antigens in vivo despite 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 Å), we characterized the biochemical and structural details of αGSA recognition by murine NKT cells. We identified a molecular switch within murine (m)CD1d that modulates NKT cell activation by αGSAs. We found that the molecular switch involves a hydrogen bond interaction between Tyr-73 of mCD1d and the amide group oxygen of αGSAs. 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 αGSAs as specific NKT cell antagonists to modulate immune responses.