8dv3

Crystal structure of human CD1b presenting Phosphatidylinositol C34:1

spinqualitylabelsall models 8dv3, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8dv3 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Ligands: 6UL, BMA, CL, EDO, FUC, IOD, MAN, NA, NAG, PIE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CD1B_HUMAN Antigen-presenting protein that binds self and non-self lipid and glycolipid antigens and presents them to T-cell receptors on natural killer T-cells. Publication Abstract from PubMed CD1 glycoproteins present lipid-based antigens to T-cell receptors (TCRs). A role for CD1b in T-cell-mediated autoreactivity was proposed when it was established that CD1b can present self-phospholipids with short alkyl chains ( approximately C34) to T cells; however, the structural characteristics of this presentation and recognition are unclear. Here, we report the 1.9 A resolution binary crystal structure of CD1b presenting a self-phosphatidylinositol-C34:1 and an endogenous scaffold lipid. Moreover, we also determined the 2.4 A structure of CD1b-phosphatidylinositol complexed to an autoreactive alphabeta TCR, BC8B. We show that the TCR docks above CD1b and directly contacts the presented antigen, selecting for both the phosphoinositol headgroup and glycerol neck region via antigen remodeling within CD1b and allowing lateral escape of the inositol moiety through a channel formed by the TCR alpha-chain. Furthermore, through alanine scanning mutagenesis and surface plasmon resonance, we identified key CD1b residues mediating this interaction, with Glu-80 abolishing TCR binding. We in addition define a role for both CD1b alpha1 and CD1b alpha2 molecular domains in modulating this interaction. These findings suggest that the BC8B TCR contacts both the presented phospholipid and the endogenous scaffold lipid via a dual mechanism of corecognition. Taken together, these data expand our understanding into the molecular mechanisms of CD1b-mediated T-cell autoreactivity. alphabeta T-cell receptor recognition of self-phosphatidylinositol presented by CD1b.,Farquhar R, Van Rhijn I, Moody DB, Rossjohn J, Shahine A J Biol Chem. 2023 Feb;299(2):102849. doi: 10.1016/j.jbc.2022.102849. Epub 2022 , Dec 29. PMID:36587766 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA