数字农科院2.0

Insights into the structural features of a feline CD8αα homodimer

文献类型: 外文期刊

作者: Rui Ying Liang;Yu Die Cao;Yong Yu Gao;Hai Yang Li;Chen Jun Sang;Yu He Xiu;Dan Li;Da Zhong Liu;Feng Shan Gao;Zi Bin Li

作者机构:

关键词: CD8αα;Crystal structure;Evolution;Feline;MHC I

期刊名称: Developmental and Comparative Immunology

ISSN: 0145-305X

年卷期: 2025 年 169 卷

页码:

收录情况: SCIE(2025版)

摘要: Cat ownership enjoys widespread popularity across the globe, with over 50 % of households in certain countries owning feline companions. Besides providing outstanding emotional support for humans, cats occupy a distinctive niche in scientific research, with their unique biological attributes and disease susceptibilities establishing them as a preferred model species across multiple disciplines. However, structural features and biological role of feline immune-related molecules remain largely unknown. In the current study, we crystallized feline CD8αα (fCD8αα) ectodomain and analyze its structural features. The fCD8αα ectodomain adopts canonical fold of the CD8αα homodimer immunoglobulin variable (Ig-V) domain and shares a common feature of CD8α also is a symbolic α-helix located on the E-F loop. In line with the known CD8αα, the homodimer formation of fCD8αα relies upon the conserved hydrophobic core,and conserved as well as species-specific residues provide additional hydrogen bonds. Compared with other known CD8α monomers, the structural differences of the fCD8α monomer focus on the loop regions linking different strands, which also show low sequence similarity in alignment analyses. Further, we generate an fCD8αα/FLA-E∗01801 model with high pLDDT and ipTM scores using AlphaFold3. Regardless of the spatial conformations of conserved or similar residues and possible interactions, the binding manner between fCD8αα and FLA-E∗01801 complex closely resembles that of the known hCD8αα/HLA-A∗0201 complex. Overall, our results provide structural and immunological knowledge for studying CD8αα function in the feline model and reveal the potential immunomodulatory roles of feline CD8 and its binding partners, deepening our understanding of the structural and functional mechanisms underlying feline immune responses.

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