The Structure and Stability of the Monomorphic HLA-G Are Influenced by the Nature of the Bound Peptide
- Monash
The highly polymorphic major histocompatibility complex class Ia (MHC-Ia) molecules present a broad array of peptides to the clonotypically diverse {alpha}{beta} 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{sup KGPPAALTL} was very similar to that of the HLA-G{sup RIIPRHLQL} structure. However, the structure of HLA-G{sup KLPQAFYIL} not only differed in the conformation of the bound peptide but also caused a small shift in the {alpha}2 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.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 1002302
- Journal Information:
- J. Mol. Biol., Vol. 397, Issue (2) ; 03, 2010; ISSN 0022-2836
- Country of Publication:
- United States
- Language:
- ENGLISH
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