9L48

Crystal structure of HLA-C*12:02-RV9

Summary for 9L48

• Entry DOI: 10.2210/pdb9l48/pdb
• Descriptor: MHC class I antigen, Beta-2-microglobulin, Toll-like receptor 9, ... (4 entities in total)
• Functional Keywords: protein complex, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 44502.16

Authors

Yang, M.,Zhong, P.L.,Wei, P.C. (deposition date: 2024-12-20, release date: 2025-03-19)

Primary citation

Yang, M.,Zhong, P.,Liu, Q.,Jiao, H.,Lei, J.,Wei, P.
Biochemical and structural insights into position 97 micropolymorphisms in human leukocyte antigen (HLA)-C*12 allotypes and their differential disease associations.
Int.J.Biol.Macromol., 306:141681-141681, 2025

PubMed Abstract: Micropolymorphisms drastically shape the antigen presentation characteristics of human leukocyte antigen class I (HLA-I) molecules, with profound implications for immune responses and disease susceptibility. HLA-C*12:02 and HLA-C*12:03 are closely related HLA-I allotypes that differ by a single amino acid substitution (R97W) but exhibit distinct associations with disease. HLA-C*12:02 has been shown to provide protective effects against HIV infection, playing a crucial role in controlling viral replication and slowing disease progression, whereas HLA-C*12:03 is associated with increased susceptibility to psoriasis. We determined the X-ray crystal structures of the two allotypes presenting MARELHPEY (MY9) and RAFPGLRYV (RV9). Peptide residues that function as anchors, as well as those accessible for T-cell antigen receptor (TCR) contact, were identified. Our results, combined with those of biochemical studies, demonstrated that the R97W variation alters the peptide-binding groove (PBG) volume and charge, leading to conformational and stability changes in pHLA-C*12 complexes and ultimately affecting peptide-binding preferences for the two HLA-C*12 allotypes. This research not only advances our understanding of the impact of HLA-I micropolymorphisms but also offers clues for the use of structure-guided therapeutics to interfere with peptide binding.

PubMed: 40044006
DOI: 10.1016/j.ijbiomac.2025.141681

Experimental method

X-RAY DIFFRACTION (1.9 Å)