PD-L2蛋白B细胞表位预测及其与PD-1结合的三维结构分析

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摘要目的：对人源程序性死亡因子1配体2（PD-L2）的B细胞表位进行预测及其与PD-1结合的三维结构分析。方法：采用生物信息学分析软件及服务器上的在线分析系统预测人类PD-L2蛋白的二级结构，柔性区域，Hopp&Woods亲水性、Zimmerman极性参数和Jameson-Wolf抗原指数以及Emini表面可及性方案等，预测结果被用以对PD-L2的优势B细胞表位区段进行多方面分析。运用抗原指数分析，预测PD-L2的B细胞表位。使用BLAST分析人源PD-L2与小鼠PD-L2的同源性，将人源PD-L2的B表位与小鼠PD-L2的序列进行匹配。将与人源PD-L2表位匹配的序列在小鼠PD-1与小鼠PD-L2的结合模型上定位，对其立体结构进行模拟，进一步直观地分析B细胞表位与蛋白结合位点的关系。结果：PD-L2的全长氨基酸序列共含有273个氨基酸，相对分子质量为31 kDa的可溶性蛋白；经综合分析，其B细胞优势表位可能为氨基酸序列N端的60～72、93～97、133～139、164～171区段。模拟立体结构分析显示表位60～72区段“QKVENDTSPHRER”位于PD-1与PD-L2的结合区域内。结论：利用生物信息学预测发现PD-L2的优势B细胞表位中，60～72、93～97、133～139、164～171区段为PD-L2的B细胞表位，其中表位60～72区段“QKVENDTSPHRER”位于PD-1与PD-L2的结合区域内。可为PD-L2抗体设计和研究提供理论基础。

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	程开
	陈旭东
	吕开绩
	金劲激
	叶晓鲜
	张丽芳
	朱冠保

关键词 ：程序性死亡因子1, 程序性死亡因子配体2, B细胞表位, 立体结构

Abstract：Objective: To predict the B-cell epitopes of human programmed death factor 1 ligand 2 (PD-L2) and to analyze its 3D structure in combination with PD-1. Methods: The secondary structure, the flexible region, the hydrophilicity of Hopp & Woods, the Zimmerman polarity parameter, the Jameson-Wolf antigen index and the Emini surface accessibility protocol of PD-L2 were predicted by bioinformatics analysis software and on-line analysis system on server. The results were used in the Multiplicative analysis of the dominant B-cell epitopes in PD-L2. Finally, using antigenic index analysis, B-cell epitopes of PD-L2 were predicted. Homology of human PD-L2 and mouse PD-L2 was analyzed by BLAST to match the B-epitopes of human PD-L2 with the sequence of mouse PD-L2. The sequences matching human PD-L2 epitopes were mapped on the binding model of mouse PD-1 and mouse PD-L2, and the stereostructure was simulated to further analyze the relationship between B cell epitopes and protein binding site. Results: The full-length amino acid sequence of PD-L2 contains a total of 273 amino acids and a molecular weight of 31 kDa soluble protein. Through comprehensive analysis, the dominant epitopes of B-cell may be the amino acid sequence of aa60-72, aa93-97, aa133-139, aa164-171 section. Simulated stereostructure analysis revealed that the epitope aa60-72 segment “QKVENDTSPHRER” is located in the binding region of PD-1 and PD-L2. Conclusion: Bioinformatics predicted that B-cell epitopes of PD-L2 in the predominant B-cell epitopes of PD-L2 were aa60-72, aa93-97, aa133-139,164-171, of which the epitope aa60-72(QKVENDTSPHRER) was located in the area where PD-1 and PD-L2 are combined. The above can provide theoretical basis for PD-L2 antibody design and research.

Key words： programmed cell death 1 programmed cell death 1 ligand 2 B-cell epitope 3D structure

收稿日期: 2017-08-08

基金资助:国家自然科学基金资助项目（81372447）；浙江省自然科学基金资助项目（Y2100660）。

通讯作者: 朱冠保，教授，硕士生导师，Email：zgbwmc@126.com。

作者简介: 程开（1991-），男，浙江温州人，硕士生。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2018/V48/I5/319

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