鳞片状细胞癌抗原Ⅰ与乙型肝炎病毒的结合受反应位点环域疏水性的影响  

Hydrophobicity of Reactive Site Loop of SCCA1 Affects its Binding to HBV

作　　者：陈敏[1] 程通[1] 许辰煜[1] 吴婷[1] 欧山海[1] 张涛[1] 张军[1] 夏宁邵[1] 

机构地区：[1]厦门大学福建省医学分子病毒学研究中心,细胞生物学与肿瘤细胞工程教育部重点实验室,厦门361005

出　　处：《生物工程学报》2005年第1期52-57,共6页Chinese Journal of Biotechnology

基　　金：教育育部跨世纪优秀人才培养计划 (2 0 0 2 )。~~

摘　　要：鳞片状细胞癌抗原Ⅰ (SCCA1)是丝氨酸蛋白酶抑制剂 (serpin)超家族的成员 ,具有多种变异体。有报道其中的两种(BP和AJ5 15 70 6 )能通过乙型肝炎病毒 (HBV)的前S1抗原促进表达SCCA1的细胞与HBV的结合。本研究从HepG2细胞中扩增出的一株SCCA1(A1)却不具备HBV结合能力。将A1的C末端与BP的C末端互换 ,获得的A1 BP能够结合HBV ,而BP A1却不能。A1与BP的C末端仅有 3个氨基酸的差异 ,其中 2个位于反应位点环域。一级结构分析发现在该区域内 ,A1的疏水性较弱 ,而BP和AJ5 15 70 6的疏水性较强。将A1的aa349位的弱疏水性的谷氨酸突变为强疏水性的缬氨酸 ,则可获得HBV结合能力。反之 ,将BP同一位点的缬氨酸突变为谷氨酸 ,则会丧失HBV结合能力。这些结果提示SCCA1与HBV的结合受反应位点环域的疏水性的影响。Squamous cell carcinoma antigen 1 (SCCA1), a member of the ovalbumin family of serine protease inhibitors, includes several variants. It was reported that expression of two SCCA1 (BP and AJ515706) in cells results in increased binding of HBV to these cells by the interaction of the expressed BP and AJ515706 with HBV pre S1 domain. In this study, a SCCA1 (A1) was isolated from HepG2, but it appears to lack this ability. A possible role of two mutants, A1 BP and BP A1, constructed by interchanging the carboxyl terminal of A1 and BP, was investigated. Cells expressing A1 BP rather than BP A1 showed an increased virus binding capacity. Comparison of A1 sequence with the sequence of BP indicated the presence of only three amino acid changes in the carboxyl terminal, two of them in the reactive site loop (RSL) of SCCA1 Primary structure analysis revealed that the hydrophobicity of BP and AJ515706 in this domain is higher than that of A1 Changing the aa349 of A1 from low hydrophobic glutamic acid to high hydrophobic valine enhanced HBV binding. In contrast, changing the aa349 of BP from valine to glutamic acid reduced HBV binding. Our finding suggests that the hydrophobicity of RSL of SCCA1 may play an important role in HBV binding to cells.

关 键 词：乙型肝炎病毒 鳞片状细胞癌抗原Ⅰ 前S1抗原 

分 类 号：R392.1[医药卫生—免疫学]