title: Structural reorganization of the antigen-binding groove of human CD1b for presentation of mycobacterial sulfoglycolipids.
abstract: The mechanisms permitting nonpolymorphic CD1 molecules to present lipid antigens that differ considerably in polar head and aliphatic tails remain elusive. It is also unclear why hydrophobic motifs in the aliphatic tails of some antigens, which presumably embed inside CD1 pockets, contribute to determinants for T-cell recognition. The 1.9-Å crystal structure of an active complex of CD1b and a mycobacterial diacylsulfoglycolipid presented here provides some clues. Upon antigen binding, endogenous spacers of CD1b, which consist of a mixture of diradylglycerols, moved considerably within the lipid-binding groove. Spacer displacement was accompanied by F' pocket closure and an extensive rearrangement of residues exposed to T-cell receptors. Such structural reorganization resulted in reduction of the A' pocket capacity and led to incomplete embedding of the methyl-ramified portion of the phthioceranoyl chain of the antigen, explaining why such hydrophobic motifs are critical for T-cell receptor recognition. Mutagenesis experiments supported the functional importance of the observed structural alterations for T-cell stimulation. Overall, our data delineate a complex molecular mechanism combining spacer repositioning and ligand-induced conformational changes that, together with pocket intricacy, endows CD1b with the required molecular plasticity to present a broad range of structurally diverse antigens.
authors: Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale, F-31077 Toulouse, France.
authors: Luis F
authors: LF
authors: Garcia-Alles
authors: Anthony
authors: A
authors: Collmann
authors: Cees
authors: C
authors: Versluis
authors: Buko
authors: B
authors: Lindner
authors: Julie
authors: J
authors: Guiard
authors: Laurent
authors: L
authors: Maveyraud
authors: Emilie
authors: E
authors: Huc
authors: Jin S
authors: JS
authors: Im
authors: Sebastiano
authors: S
authors: Sansano
authors: Thérèse
authors: T
authors: Brando
authors: Sylviane
authors: S
authors: Julien
authors: Jacques
authors: J
authors: Prandi
authors: Martine
authors: M
authors: Gilleron
authors: Steven A
authors: SA
authors: Porcelli
authors: Henri
authors: H
authors: de la Salle
authors: Albert J R
authors: AJ
authors: Heck
authors: Lucia
authors: L
authors: Mori
authors: Germain
authors: G
authors: Puzo
authors: Lionel
authors: L
authors: Mourey
authors: Gennaro
authors: G
authors: De Libero
mesh_terms: D018949:Antigens, CD1 / Q000737:chemistry* / Q000378:metabolism; D002855:Chromatography, Thin Layer; D018360:Crystallography, X-Ray; D005583:Fourier Analysis; D006017:Glycolipids / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D016296:Mutagenesis; D009169:Mycobacterium tuberculosis / Q000737:chemistry*; D011487:Protein Conformation; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D018949:Antigens, CD1; C419394:CD1b antigen; D006017:Glycolipids; C011117:sulfoglycolipids