Structural highlights
Function
[B2MG_MACMU] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system (By similarity).
Publication Abstract from PubMed
Similar to host proteins, N-myristoylation occurs for viral proteins to dictate their pathological function. However, this lipid-modifying reaction creates a novel class of "lipopeptide" Ags targeted by host CTLs. The primate MHC class I-encoded protein, Mamu-B*098, was previously shown to bind N-myristoylated 5-mer peptides. Nevertheless, T cells exist that recognize even shorter lipopeptides, and much remains to be elucidated concerning the molecular mechanisms of lipopeptide presentation. We, in this study, demonstrate that the MHC class I allele, Mamu-B*05104, binds the N-myristoylated 4-mer peptide (C14-Gly-Gly-Ala-Ile) derived from the viral Nef protein for its presentation to CTLs. A phylogenetic tree analysis indicates that these classical MHC class I alleles are not closely associated; however, the high-resolution x-ray crystallographic analyses indicate that both molecules share lipid-binding structures defined by the exceptionally large, hydrophobic B pocket to accommodate the acylated glycine (G1) as an anchor. The C-terminal isoleucine (I4) of C14-Gly-Gly-Ala-Ile anchors at the F pocket, which is distinct from that of Mamu-B*098 and is virtually identical to that of the peptide-presenting MHC class I molecule, HLA-B51. The two central amino acid residues (G2 and A3) are only exposed externally for recognition by T cells, and the methyl side chain on A3 constitutes a major T cell epitope, underscoring that the epitopic diversity is highly limited for lipopeptides as compared with that for MHC class I-presented long peptides. These structural features suggest that lipopeptide-presenting MHC class I alleles comprise a distinct MHC class I subset that mediates an alternative pathway for CTL activation.
Identification and Structure of an MHC Class I-Encoded Protein with the Potential to Present N-Myristoylated 4-mer Peptides to T Cells.,Yamamoto Y, Morita D, Shima Y, Midorikawa A, Mizutani T, Suzuki J, Mori N, Shiina T, Inoko H, Tanaka Y, Mikami B, Sugita M J Immunol. 2019 Jun 15;202(12):3349-3358. doi: 10.4049/jimmunol.1900087. Epub, 2019 May 1. PMID:31043477[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yamamoto Y, Morita D, Shima Y, Midorikawa A, Mizutani T, Suzuki J, Mori N, Shiina T, Inoko H, Tanaka Y, Mikami B, Sugita M. Identification and Structure of an MHC Class I-Encoded Protein with the Potential to Present N-Myristoylated 4-mer Peptides to T Cells. J Immunol. 2019 Jun 15;202(12):3349-3358. doi: 10.4049/jimmunol.1900087. Epub, 2019 May 1. PMID:31043477 doi:http://dx.doi.org/10.4049/jimmunol.1900087
