| 引用本文: | 王彩翠,毛甜甜,裘天颐,汪源,郑根徽,曹志伟.从新冠Spike蛋白抗原抗体复合物探究表位与抗体的空间识别关系[J].中国现代应用药学,2022,39(21):2850-2855. |
| WANG Caicui,MAO Tiantian,QIU Tianyi,WANG Yuan,ZHENG Genhui,CAO Zhiwei.Exploring the Spatial Recognition Relationship Between Epitopes and Antibodies from SARS-CoV-2 Spike Protein-antibody Complexes[J].Chin J Mod Appl Pharm(中国现代应用药学),2022,39(21):2850-2855. |
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| 从新冠Spike蛋白抗原抗体复合物探究表位与抗体的空间识别关系 |
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王彩翠1, 毛甜甜1, 裘天颐2, 汪源1, 郑根徽1, 曹志伟1,3
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1.同济大学生命科学与技术学院, 上海 200092;2.复旦大学附属中山医院, 上海 200032;3.复旦大学生命科学学院, 上海 200433
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| 摘要: |
| 目的 基于新冠Spike蛋白抗原抗体复合物结构数据，探究表位与抗体的空间识别关系。方法 基于718对新冠Spike蛋白抗原抗体复合物结构数据，首先分析抗原表位分布的热点区域及抗体基因片段使用偏好性；其次对抗原抗体结合界面提取抗原空间表位和CDR结构，分别构建抗原空间表位的相似性聚类树以及对应抗体重链CDR结构的相似性聚类树，通过比较对应聚类树之间的相似性评估抗原空间表位与抗体CDR结构的整体识别关系。结果 表位位点中94.02%分布于RBD，4.44%分布于NTD，且前10位热点位置均分布于RBM；抗体VJ基因的偏好性片段为IGHV3-30/IGHJ4和IGHV1-58/IGHJ3。空间表位聚类树与对应抗体CDR结构聚类树之间的相似性显著高于随机聚类树，提示表位与CDR结构存有内在关联。进一步分析数据发现，免疫原性相似的抗原表位，会被结构相似的CDR结构识别，且CDR3结构的贡献最大。结论 从目前数据来看，表位位点分布以RBD区域为主，抗体IGHV3-30/IGHJ4和IGHV1-58/IGHJ3片段突出，相似的抗原空间表位会被相似的CDR结构识别，这些发现为后续的新冠病毒抗体设计及优化提供一定的理论支撑。 |
| 关键词: 抗原表位 抗体 CDR 层次聚类 SARS-CoV-2 |
| DOI：10.13748/j.cnki.issn1007-7693.2022.21.022 |
| 分类号:R914.2 |
| 基金项目:国家自然科学基金项目(32070657) |
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| Exploring the Spatial Recognition Relationship Between Epitopes and Antibodies from SARS-CoV-2 Spike Protein-antibody Complexes |
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WANG Caicui1, MAO Tiantian1, QIU Tianyi2, WANG Yuan1, ZHENG Genhui1, CAO Zhiwei1,3
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1.School of Life Sciences and Technology, Tongji University, Shanghai 200092, China;2.Zhongshan Hospital, Fudan University, Shanghai 200032, China;3.School of Life Sciences, Fudan University, Shanghai 200433, China
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| Abstract: |
| OBJECTIVE To explore the spatial recognition relationship between epitopes and antibodies based on the structure data of SARS-CoV-2 Spike protein antigen-antibody complex. METHODS Seven hundred and eighteen available SARS-CoV-2 antigen-antibody structural complexes were analyzed in multiple ways. Firstly, the epitope hotspots and the usage preference of antibody gene fragments were analyzed. Secondly, the spatial epitopes and CDR structures were extracted from the antigen-antibody binding interfaces, and clustering trees of the spatial epitopes and the antibody CDR structures were respectively constructed. The recognition relationship between the epitopes and the CDR structures was evaluated by comparing the similarity between the corresponding clustering trees. RESULTS The 94.02% epitope sites were mapped on RBD, and 4.44% on NTD, with the top10 hotspots being all located in RBM. The most common antibody VJ genes were identified as IGHV3-30/IGHJ4 and IGHV1-58/IGHJ3. The similarity between the clustering trees of spatial epitopes and those of the corresponding antibody CDR structures was significantly higher than that expected from random clustering trees, suggesting an intrinsic epitope-CDR matching. Further analysis of the data revealed that the epitopes with similar immunogenicity would be recognized by similar CDR structures, with CDR3 domain making the greatest contribution. CONCLUSION The current data identifies that the epitopes are concentrated in its RBD region while the IGHV3-30/IGHJ4 and IGHV1-58/IGHJ3 are the preferred VJ gene combination utilized for the production of Spike protein-targeting antibodies. It also suggests that similar epitopes are likely to be recognized by similar CDR structures. Collectively, these findings add a new theoretical basis for the SARS-CoV-2 antibody design and optimization. |
| Key words: epitope antibody CDR hierarchical clustering SARS-CoV-2 |
