8kb0

Publication Abstract from PubMed

Micropolymorphism significantly shapes the peptide-binding characteristics of major histocompatibility complex class I (MHC-I) molecules, affecting the host's resistance to pathogens, which is particularly pronounced in avian species displaying the "minimal essential MHC" expression pattern. In this study, we compared two duck MHC-I alleles, Anpl-UAA*77 and Anpl-UAA*78, that exhibit markedly different peptide binding properties despite their high sequence homology. Through mutagenesis experiments and crystallographic analysis of complexes with the influenza virus-derived peptide AEAIIVAMV (AEV9), we identified a critical role for the residue at position 62 in regulating hydrogen-bonding interactions between the peptide backbone and the peptide-binding groove. This modulation affects the characteristics of the B pocket and the stability of the loop region between the 3(10) helix and the alpha1 helix, leading to significant changes in the structure and stability of the peptide-MHC-I complex (pMHC-I). Moreover, the proportion of different residues at position 62 among Anpl-UAAs may reflect the correlation between pAnpl-UAA stability and duck body temperature. This research not only advances our understanding of the Anpl-UAA structure but also deepens our insight into the impact of MHC-I micropolymorphism on peptide binding.

The impact of micropolymorphism in Anpl-UAA on structural stability and peptide presentation.,Tang Z, Wang S, Du L, Hu D, Chen X, Zheng H, Ding H, Chen S, Zhang L, Zhang N Int J Biol Macromol. 2024 May;267(Pt 2):131665. doi: , 10.1016/j.ijbiomac.2024.131665. Epub 2024 Apr 16. PMID:38636758^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.