人N-甲基-D-门冬氨酸受体主亚基受体激活相关多肽的理化特性与抗原性分析  

Antigenicity and physicochemical properties of two human NR1a polypeptides related to activation of NMDA receptor

作　　者：孙长凯[1] 赵杰[2] 李伍举[1] 冯健男[1] 刘淑红[1] 朱克[3] 王吉庆[4] 尹安民[4] 韩大跃[4] 张万琴[2] 姜潮[2] 姜长斌[2] 聂志余[2] 王耀山[5] 包礼平[2] 范明[1] 

机构地区：[1]军事医学科学院基础医学研究所,北京100850 [2]大连医科大学脑疾病研究所 [3]解放军总医院神经病学研究所 [4]解放军第二一○医院 [5]沈阳军区总医院神经科

出　　处：《中华医学杂志》2002年第1期50-53,共4页National Medical Journal of China

基　　金：国家自然科学基金资助项目 (3 0 0 70 2 67) ;中国博士后科学基金资助项目 (2 0 0 1)

摘　　要：目的　分析人N 甲基 D 门冬氨酸受体 (NMDAR)主亚基NR1a上两个受体激活相关多肽P1、P2的抗原性及其理化特性。方法　用GOLDKEY软件从蛋白质数据库中调出人NR1a分子的氨基酸序列 ,分别在其第一、第三跨膜域前后逆向、顺向截取 15 1和 14 4个氨基酸长度的多肽片段P1与P2 ,选取Hopp&Woods与Kyte亲水性、Janin表面可及性、Karplus Schulz主链柔韧性及Welling抗原性等参数予以多参数分析 ,采用Prosite程序与Chou Fasman方法比较其氨基酸位点与二级结构特征 ,以此为基础综合判定P1与P2片段的抗原位点并与已有的实验结果相比较。结果　P1、P2多肽片段上可能分别有 6和 7个 8～ 15aa长序列具有良好的抗原性。P1相关序列主要分布于其氨基端 ,与配体结合关键氨基酸残基相距较远。P2上的相关序列分布较均匀 ,包含有受体激活重要相关位点或与配体结合关键氨基酸残基距离较近。P2片段的总体抗原性、亲水性与可及性均强于P1,尤以其近膜的 15个残基为著。P1、P2多肽片段均含有一定数量的 β 转角 ,但P1片段含有较多的半胱氨酸残基和无规卷曲 ,而P2片段则含有较多的芳香族残基并以α螺旋结构为主。结论　人NMDAR主亚基NR1a上的两个受体激活相关多肽P1、P2均具有一定数量的抗原位点 ,与P1相比较 ,P2可能更易成为NMDAR免?Objective To investigate the distribution of antigenic sites in two human NR1a polypeptides related to activation of N methyl D aspartate receptor (NMDAR) and their physicochemical properties. Methods The amino acid sequences of two polypeptides, P1, a region containing 151 amino acid residues preceding the first transmembrane domain of the human NR1a, and P2 with 144 residues following the third transmembrane domain, were obtained from protein database by GOLDKEY software (4.0 version). Four parameters including Hopp Woods and Kyte hydrophilicity,Janin accessibility, Karplus Schulz flexibility, and Welling antigenicity were used to determine the antigenic sites, and Prosite programme and Chou Fasman method were employed to analyze their related sequence motifs and the secondary structures. Finally, comparison of the comprehensive predictions with some of the available experimental information was made. Results There were about six and seven antigenic sites containing 8～15 residues in the P1 and P2 polypeptides respectively. The antigenic sites in P1 were mainly located in the amino terminal, but the ones in P2 were dispersed rather uniformly. Many sites in P2 polypeptide including some residues in its initial part, the amino terminal, showed higher hydrophilicity, accessibility, and antigenicity than those in P1. In addition, P1 and P1 were also different in the primary and secondary structure. P1 contained more cysteine residues and was rich in random coils, while P2 contained more aromatic residues and exhibited mainly helical structures. Conclusion Both human NR1a polypeptides related to activation of NMDA receptor, P1 and P2, have a certain amount of antigenic sites. Compared with P1, P2 may be of higher antigenicity, and may be more easily used as a molecular target in immunization intervention to control the activation of NMDAR.

关 键 词：神经免疫调节 抗原 多肽片段P1 多肽片段P2 氨基酸类 人N-甲基-D-门冬氨酸受体 

分 类 号：R741.02[医药卫生—神经病学与精神病学]