9l4h

Crystal structure of HLA-C*14:03 complexed with KIR2DL2

spinqualitylabelsall models 9l4h, resolution 3.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9l4h is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.1Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A6F8VJ76_HUMAN Involved in the presentation of foreign antigens to the immune system.[ARBA:ARBA00002297] Publication Abstract from PubMed Micropolymorphisms in human leukocyte antigen class I (HLA-I) molecules critically influence antigen presentation and immune recognition. Most studies have focused on variations within the peptide-binding groove (PBG), neglecting the potential impact of residues located outside this region. HLA-C*14:02 and HLA-C*14:03 differ only at position 21 (R21 and H21, respectively), which is situated outside the PBG, yet these two allotypes exhibit distinct clinical associations with HIV control in the context of KIR2DL2, an inhibitory killer cell immunoglobulin-like receptor that modulates natural killer (NK) cell activity. Here, we investigated the molecular mechanisms by which the R21H micropolymorphism shapes immune responses. Structural and biochemical analyses revealed that position 21 indirectly regulates the conformation of the B pocket within the PBG, significantly affecting HLA-C*14 stability and altering the composition of its peptide repertoire, while preserving core peptide motifs and recognition by KIR2DL2. Notably, the R21H variation is evolutionarily conserved across various HLA-I molecules and exhibits similar interactions with neighboring residues, suggesting a broadly conserved role in structural stability and immune regulation. These findings suggest that the stability differences between HLA-C*14 allotypes may influence their differential clinical associations, highlighting the previously underappreciated role of micropolymorphisms outside the PBG in modulating immune responses. Micropolymorphism outside the peptide-binding groove of human leukocyte antigen (HLA)-C*14 modulates structural stability and shapes immune responses.,Liu Q, Yang M, Zhong P, Wei Q, Jiao H, Meng J, Ding L, Zhu X, Wei P Int J Biol Macromol. 2025 May;309(Pt 1):142772. doi: , 10.1016/j.ijbiomac.2025.142772. Epub 2025 Apr 2. PMID:40185448 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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