title: Association of beta2-microglobulin with the alpha3 domain of H-2Db heavy chain.
abstract: MHC class I molecules are heterotrimeric complexes composed of heavy chain, beta2-microglobulin (beta2m) and short peptide. This trimeric complex is generated in the endoplasmic reticulum (ER), where a peptide loading complex (PLC) facilitates transport from the cytosol and binding of the peptide to the preassembled ER resident heavy chain/beta2m dimers. Association of mouse MHC class I heavy chain with beta2m is characterized by allelic differences in the number and/or positions of amino acid interactions. It is unclear, however, whether all alleles follow common binding patterns with minimal contributions by allele-specific contacts, or whether essential contacts with beta2m are different for each allele. While searching for the PLC binding site in the alpha3 domain of the mouse MHC class I molecule H-2Db, we unexpectedly discovered a site critical for binding mouse, but not human, beta2m. Interestingly, amino acids in the corresponding region of another MHC class I heavy chain allele do not make contacts with the mouse beta2m. Thus, there are allelic differences in the modes of binding of beta2m to the heavy chain of MHC class I.
authors.affiliation: Michael Heidelberger Division of Immunology, Department of Pathology and NYU Cancer Center, NYU School of Medicine, New York, NY 10016, USA.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Lilić
authors.forename: Zoran
authors.initials: Z
authors.lastname: Popmihajlov
authors.forename: John J
authors.initials: JJ
authors.lastname: Monaco
authors.forename: Stanislav
authors.initials: S
authors.lastname: Vukmanović
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D002417:Cattle; D006183:H-2 Antigens / Q000235:genetics / Q000378:metabolism*; D064532:Histocompatibility Antigen H-2D; D006801:Humans; D051379:Mice; D017354:Point Mutation; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism*; D001613:beta 2-Microglobulin / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D011993:Recombinant Fusion Proteins; D001613:beta 2-Microglobulin