9UL1

Crystal structure of Tibetan wild boar SLA-1*Z0301 for 2.32 angstrom

Summary for 9UL1

• Entry DOI: 10.2210/pdb9ul1/pdb
• Descriptor: MHC class I antigen, Beta-2-microglobulin, ALA-LEU-LEU-SER-SER-LYS-THR-SER-VAL (3 entities in total)
• Functional Keywords: mhc, immunology, immune system, antiviral protein
• Biological source: Sus scrofa (pig); More
• Total number of polymer chains: 3
• Total formula weight: 44215.24

Authors

Fan, S.,Wang, Y. (deposition date: 2025-04-18, release date: 2025-08-13)

Primary citation

Fan, S.,Kang, C.,Peng, J.,Wang, T.,Ren, S.,Li, J.,Li, L.,Wu, C.,Wang, Y.,Li, L.
Structural basis of Tibetan wild boar SLA-1*Z0301 reveals conserved peptide presentation and potential high-altitude adaptation.
Int.J.Biol.Macromol., 320:145933-145933, 2025

PubMed Abstract: Major Histocompatibility Complex (MHC) class I molecules facilitate antiviral immunity through their polymorphic peptide-binding diversity. Tibetan wild boars, adapted to extreme plateau conditions, exhibit enhanced disease resistance. Here, we present the first three-dimensional structure of the Tibetan wild boar SLA-1*Z0301 in complex with the GP3-ALL9 peptide derived from porcine reproductive and respiratory syndrome virus (PRRSV). Using X-ray crystallography and AlphaFold3 modeling, we characterized the peptide-binding motif of SLA-1*Z0301, which shares conserved binding pockets with SLA-1*08 alleles found in various domestic pigs, indicating convergent peptide presentation across wild and domestic swine lineages. Thermal stability assays revealed that the primary anchors of SLA-1*Z0301-P2 (B pocket, Tm = 42.5 °C) and P9 (F pocket, Tm = 47.6 °C)-exhibited greater stability compared to mutants in the Heishan pig SLA-3*hs0202 (P3-A = 40.0 °C, P9-A = 38.3 °C), suggesting structural adaptations to high-altitude conditions. A genome-wide screening identified 125 nonapeptides from PRRSV-1 and PRRSV-2 that conform to the SLA-1*Z0301 motif, spanning structural (GP2-GP5) and nonstructural proteins. Notably, five epitopes overlapped with immunodominant responses observed in Large White and Yorkshire × Landrace, highlighting conserved antigen presentation across wild and domestic swine lineages. These results provide valuable insights into the development of cross-species antiviral strategies and vaccine design.

PubMed: 40653219
DOI: 10.1016/j.ijbiomac.2025.145933

Experimental method

X-RAY DIFFRACTION (2.323 Å)