Structural basis of a high-affinity antibody binding to glycoprotein region with consecutive glycosylation sites

doi:10.1101/2022.07.24.501275

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	Structural basis of a high-affinity antibody binding to glycoprotein region with consecutive glycosylation sites
	Han, Y.-b 1,2; Niu, J.1 ; Pan, D.3; Feng, C.-c 3; Song, K.1 ; Meng, B.1 ; Westerlind, U.4; Zhang, Y.5; Liu, H.-g 6; Xu, L.1,7 ; Zhou, D.-p 3
	2022-07-24
状态	已发表
摘要	Consecutive glycosylation sites occur in both self and viral proteins. Glycan-shielding of underneath peptide region is a double-edged sword, that avoids immune attack to self proteins, but helps viruses including HIV-1 and SARS-CoV2 to escape antibody binding. Here we report a high-affinity antibody, 16A, binding to linear peptide containing consecutive glycosylation sites. Co-crystallization of 16A Fab and glycopeptides with GalNAc modifications at different sites showed that STAPPAHG is the sequence recognized by 16A antibody. GalNAc modification at Threonine site on STAPPAHG sequence significantly increased the affinity of Fab binding by 30.6 fold (KD=6.7nM). The increased affinity is conferred by hydrophilic and pi-stacking interactions between the GalNAc residue on Threonine site and a Trp residue from the CDR1 region of the heavy chain. Furthermore, molecular modeling suggested that GalNAc on T site causes more favorable conformation for antibody binding. These results showed that glycan modification most proximal to linear peptide core epitope significantly increases antigenicity of a glycopeptide epitope. The antibody recognition mode by peptide-binding CDR groove with a glycan-binding edge, may shed light on designing of linear glycopeptide-based vaccines for cancer and viral diseases.
语种	英语
DOI	10.1101/2022.07.24.501275
相关网址	查看原文
出处	bioRxiv
收录类别	PPRN.PPRN
WOS记录号	PPRN:11202878
WOS类目	Immunology
资助项目	National Key Research and Development Plan grants["2021YEE0200500","22120200163","15002360172","PWYgy2018–10","2017M610281"] ; Fundamental Research Funds for the Central Universities[2017YFA0505901]
文献类型	预印本
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/348566
专题	免疫化学研究所免疫化学研究所_公共科研平台 iHuman研究所_PI研究组_刘志杰组生命科学与技术学院_博士生免疫化学研究所_公共科研平台_生物医学大数据平台
通讯作者	Xu, L.; Zhou, D.-p
作者单位	1.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China 2.Nanjing Univ Chinese Med, Sch Pharm, State Key Lab Cultivat Base TCM Qual & Efficacy, Nanjing 210023, Peoples R China 3.Tongji Univ Sch Med, Shanghai 200092, Peoples R China 4.Umea Univ, Dept Chem, S-90187 Umea, Sweden 5.Shanghai Jiao Tong Univ, Shanghai Ctr Syst Biomed, Key Lab Syst Biomed, Minist Educ, 800 Dongchuan Rd, Shanghai 200240, Peoples R China 6.Beijing Computat Sci Res Ctr, Complex Syst Div, ZPark2, Haidian 100193, Beijing, Peoples R China 7.Global Hlth Drug Discovery Inst, Haidian 100192, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Han, Y.-b,Niu, J.,Pan, D.,et al. Structural basis of a high-affinity antibody binding to glycoprotein region with consecutive glycosylation sites. 2022.