糖基化
抗体
聚糖
体细胞突变
天冬酰胺
生物
计算生物学
糖蛋白
遗传学
B细胞
氨基酸
作者
Marcella Nunes Melo‐Braga,Milene Barbosa Carvalho,Manuela Cristina Emiliano Ferreira,Jason J. Lavinder,Abdolrahim Abbasi,Giuseppe Palmisano,Morten Thaysen‐Andersen,Mohammad M. Sajadi,Gregory C. Ippolito,Liza Felicori
标识
DOI:10.1016/j.ijbiomac.2023.128362
摘要
N-glycosylation at the antibody variable domain has emerged as an important modification influencing antibody function. Despite its significance, information regarding its role and regulation remains limited. To address this gap, we comprehensively explored antibody structures housing N-glycosylation within the Protein Data Bank, yielding fresh insights into this intricate landscape. Our findings revealed that among 208 structures, N-glycosylation was more prevalent in human and mouse antibodies containing IGHV1–8 and IGHV2–2 germline genes, respectively. Moreover, our research highlights the potential for somatic hypermutation to introduce N-glycosylation sites by substituting polar residues (Ser or Thr) in germline variable genes with asparagine. Notably, our study underscores the prevalence of N-glycosylation in antiviral antibodies, especially anti-HIV. Besides antigen-antibody interaction, our findings suggest that N-glycosylation may impact antibody specificity, affinity, and avidity by influencing Fab dimer formation and complementary-determining region orientation. We also identified different glycan structures in HIV and SARS-CoV-2 antibody proteomic datasets, highlighting disparities from the N-glycan structures between PDB antibodies and biological repertoires further highlighting the complexity of N-glycosylation patterns. Our findings significantly enrich our understanding of the N-glycosylation's multifaceted characteristics within the antibody variable domain. Additionally, they underscore the pressing imperative for a more comprehensive characterization of its impact on antibody function.
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