title: The structure and stability of the monomorphic HLA-G are influenced by the nature of the bound peptide.
abstract: The highly polymorphic major histocompatibility complex class Ia (MHC-Ia) molecules present a broad array of peptides to the clonotypically diverse alphabeta T-cell receptors. In contrast, MHC-Ib molecules exhibit limited polymorphism and bind a more restricted peptide repertoire, in keeping with their major role in innate immunity. Nevertheless, some MHC-Ib molecules do play a role in adaptive immunity. While human leukocyte antigen E (HLA-E), the MHC-Ib molecule, binds a very restricted repertoire of peptides, the peptide binding preferences of HLA-G, the class Ib molecule, are less stringent, although the basis by which HLA-G can bind various peptides is unclear. To investigate how HLA-G can accommodate different peptides, we compared the structure of HLA-G bound to three naturally abundant self-peptides (RIIPRHLQL, KGPPAALTL and KLPQAFYIL) and their thermal stabilities. The conformation of HLA-G(KGPPAALTL) was very similar to that of the HLA-G(RIIPRHLQL) structure. However, the structure of HLA-G(KLPQAFYIL) not only differed in the conformation of the bound peptide but also caused a small shift in the alpha2 helix of HLA-G. Furthermore, the relative stability of HLA-G was observed to be dependent on the nature of the bound peptide. These peptide-dependent effects on the substructure of the monomorphic HLA-G are likely to impact on its recognition by receptors of both innate and adaptive immune systems.
authors.affiliation: The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Walpole
authors.forename: Lars
authors.initials: L
authors.lastname: Kjer-Nielsen
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Kostenko
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Brooks
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.forename: Craig S
authors.initials: CS
authors.lastname: Clements
mesh_terms: D018360:Crystallography, X-Ray; D006680:HLA Antigens / Q000737:chemistry* / Q000378:metabolism*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D055550:Protein Stability; D020836:Protein Structure, Quaternary; D013696:Temperature
chemical_list: D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I