9wj4

Crystal structure of rhesus macaque MHC class I molecule Mamu-B*05104 complexed with C14-Gly1-Gly2-Ser3-Ile4 lipopeptide

spinqualitylabelsall models 9wj4, resolution 2.04Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9wj4 is a 3 chain structure with sequence from Macaca mulatta and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.04Å Ligands: EDO, MES, MYR, NA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function B2ZHY7_MACMU Publication Abstract from PubMed A fraction of the major histocompatibility complex class I proteins can bind N-myristoylated short lipopeptides rather than conventional long peptides. The molecular mechanisms underlying lipopeptide antigen presentation were recently delineated for N-myristoylated 4-mer lipopeptides (C14-Gly1-Gly2-Ala3-Ile4; C14nef4) derived from the retroviral Nef protein. The C14nef4 lipopeptides are captured by the rhesus major histocompatibility complex class I allomorph, Mamu-B *05104, and recognized by specific alphabeta T-cell receptors (TCRs). The crystal structure of the Mamu-B *05104-C14nef4-TCR complex indicates that both ends of C14nef4, namely, myristic acid and C-terminal Ile4, are anchored at the antigen-binding groove, leaving Gly1, Gly2, and Ala3 exposed. Among these residues, only the amide bond of Gly1 forms a hydrogen bond with TCRs and serves as a primary T-cell epitope. However, it remains unclear how antigenic and nonantigenic lipopeptides exist, both of which share the primary T-cell epitope. To gain insight into this enigma, we utilized C14nef4 and its analogs with an amino acid substitution for Ala3. Biolayer interferometry experiments with immobilized TCRs and lipopeptide-bound Mamu-B *05104 indicated that the antigenic strength varied among these lipopeptides. The crystal structures of Mamu-B *05104 complexed with either C14nef4 or each of its five analogs showed a downward shift in the proximal part (C(1)-C(4) carbons) of the hydrocarbon chain and the linked Gly1 residue for poorly antigenic analogs. Furthermore, molecular dynamics simulations indicated that lipopeptide ligands alter their conformation dynamically, with differential efficiency in exposing Gly1 externally. Thus, the antigenic strength of lipopeptides is affected by their intrinsic ability to sustain a T-cell epitope-exposed configuration. Lipopeptide ligands captured by MHC class I molecules undergo dynamic conformational changes that affect their antigenic strength.,Morita D, Fujii T, Inuki S, Suzuki H, Mikami B, Sugita M J Biol Chem. 2026 Feb;302(2):111049. doi: 10.1016/j.jbc.2025.111049. Epub 2025 , Dec 12. PMID:41391759 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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