title: The 2.5 Å structure of CD1c in complex with a mycobacterial lipid reveals an open groove ideally suited for diverse antigen presentation.
abstract: CD1 molecules function to present lipid-based antigens to T cells. Here we present the crystal structure of CD1c at 2.5 Å resolution, in complex with the pathogenic Mycobacterium tuberculosis antigen mannosyl-β1-phosphomycoketide (MPM). CD1c accommodated MPM's methylated alkyl chain exclusively in the A' pocket, aided by a unique exit portal underneath the α1 helix. Most striking was an open F' pocket architecture lacking the closed cavity structure of other CD1 molecules, reminiscent of peptide binding grooves of classical major histocompatibility complex molecules. This feature, combined with tryptophan-fluorescence quenching during loading of a dodecameric lipopeptide antigen, provides a compelling model by which both the lipid and peptide moieties of the lipopeptide are involved in CD1c presentation of lipopeptides.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Louise
authors.initials: L
authors.lastname: Scharf
authors.forename: Nan-Sheng
authors.initials: NS
authors.lastname: Li
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Hawk
authors.forename: Diana
authors.initials: D
authors.lastname: Garzón
authors.forename: Tejia
authors.initials: T
authors.lastname: Zhang
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Fox
authors.forename: Allison R
authors.initials: AR
authors.lastname: Kazen
authors.forename: Sneha
authors.initials: S
authors.lastname: Shah
authors.forename: Esmael J
authors.initials: EJ
authors.lastname: Haddadian
authors.forename: Jenny E
authors.initials: JE
authors.lastname: Gumperz
authors.forename: Alan
authors.initials: A
authors.lastname: Saghatelian
authors.forename: José D
authors.initials: JD
authors.lastname: Faraldo-Gómez
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Meredith
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Piccirilli
authors.forename: Erin J
authors.initials: EJ
authors.lastname: Adams
mesh_terms: D017951:Antigen Presentation; D000940:Antigenic Variation; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000276:immunology; D018949:Antigens, CD1 / Q000737:chemistry* / Q000276:immunology; D003001:Cloning, Molecular; D019295:Computational Biology; D003460:Crystallization; D006023:Glycoproteins / Q000737:chemistry* / Q000276:immunology; D006649:Histocompatibility Antigens / Q000378:metabolism; D006801:Humans; D018448:Models, Immunological; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D014965:X-Rays
chemical_list: D000942:Antigens, Bacterial; D018949:Antigens, CD1; C437944:CD1C protein, human; D006023:Glycoproteins; D006649:Histocompatibility Antigens; D010446:Peptide Fragments