9EB6

Chicken YF1.7*1 presenting myristoylated peptide derived from tegument protein CIRC

Summary for 9EB6

• Entry DOI: 10.2210/pdb9eb6/pdb
• Descriptor: MHC Rfp-Y class I alpha chain, Beta-2-microglobulin, Peptide derived from tegument protein CIRC, ... (9 entities in total)
• Functional Keywords: chicken, antigen presentation, lipopeptide, mhc-like, tegument, marek's disease virus, mdv, immune system
• Biological source: Gallus gallus (chicken); More
• Total number of polymer chains: 3
• Total formula weight: 43257.80

Authors

Khandokar, Y.,Wang, C.J.H.,Rossjohn, J.,Le Nours, J. (deposition date: 2024-11-11, release date: 2025-07-23)

Primary citation

Khandokar, Y.,Cheng, T.Y.,Wang, C.J.H.,Cao, T.P.,Nagampalli, R.S.K.,Sivaraman, K.K.,Van Rhijn, I.,Rossjohn, J.,Moody, D.B.,Nours, J.L.
Molecular basis for presentation of N-myristoylated peptides by the chicken YF1∗7.1 molecule.
J.Biol.Chem., 301:110253-110253, 2025

PubMed Abstract: Major histocompatibility complex I (MHC-I) and MHC-I-like molecules play a central role in mediating immunity. Through their conservation across all taxa of jawed vertebrates, the MHC-I-like proteins have adapted to present non-peptidic antigens to distinct T cell populations. While our understanding of the structure-function relationship of MHC-I and MHC-I-like molecules in humans and mice is well established, the nature of the antigens presented by MHC-I- like molecules in "non-model" species remains unclear. Here, using a mammalian recombinant expression system combined with mass spectrometry approaches, we identified N-myristoylated peptides as endogenous ligands for the chicken MHC-I-like protein YF1∗7.1. Given the importance of N-myristoylation in viral pathogenesis, we determined the crystal structure of YF1∗7.1 in complex with two N-myristoylated peptides derived from Marek's disease virus (MDV), demonstrating the molecular basis that underpins the presentation of N-myristoylated peptides from MDV, a highly contagious and fatal viral neoplastic disease in chickens. Thus, the identified ligands are distinct from unmodified peptides found in classical MHC-I and -II as well as diverse amphipathic lipids captured by CD1 proteins. Collectively, our study lays the foundation for further molecular and functional characterization of YF1∗7.1 and more broadly of the role of the MHC-I encoded by the MHC-Y gene cluster in protection against highly contagious viral neoplastic diseases in chickens.

PubMed: 40412526
DOI: 10.1016/j.jbc.2025.110253

Experimental method

X-RAY DIFFRACTION (1.9 Å)