6IWG

Crystal structure of rhesus macaque MHC class I molecule Mamu-B*05104 complexed with N-myristoylated 4-mer lipopeptide derived from SIV nef protein

Summary for 6IWG

• Entry DOI: 10.2210/pdb6iwg/pdb
• Descriptor: MHC class I antigen, Beta-2-microglobulin, N-myristoylated 4-mer lipopeptide, ... (7 entities in total)
• Functional Keywords: antigen presentation, major histocompatibility complex, n-myristoylation, aids, nef, immune system
• Biological source: Macaca mulatta (Rhesus macaque); More
• Total number of polymer chains: 3
• Total formula weight: 45571.65

Authors

Yamamoto, Y.,Morita, D.,Sugita, M. (deposition date: 2018-12-05, release date: 2019-08-14, Last modification date: 2023-11-22)

Primary citation

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 PresentN-Myristoylated 4-mer Peptides to T Cells.
J Immunol., 202:3349-3358, 2019

PubMed Abstract: Similar to host proteins, -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 -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 -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.

PubMed: 31043477
DOI: 10.4049/jimmunol.1900087

Experimental method

X-RAY DIFFRACTION (1.8 Å)