Role of CD4 hinge region in GP120 utilization by immunoglobulin domain 1.
Role of CD4 hinge region in GP120 utilization by immunoglobulin domain 1.
复制标题
CD4 铰链区在免疫球蛋白结构域 1 利用 GP120 中的作用。
DOI：
10.1006/bbrc.2002.6677
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发表时间：
2002
影响因子：
3.1
通讯作者：
Peiper,StephenC
中科院分区：
文献类型：
--
作者：
Murray,JamesL;Hu,Qin-xue;Navenot,Jean-Marc;Peiper,StephenC
CD 4的免疫球蛋白样结构域1（D1-CD 4）通过结合包膜糖蛋白（ENV）并暴露其辅助受体结合位点来促进HIV感染。为了研究CD 4-ENV-辅助受体的相互作用，我们表征了具有CD 4的结构域1和2（D1 D2-CD 4）的杂交受体，所述结构域1和2连接到趋化因子受体CCR 5、CXCR 4、CXCR 2和DARC的N末端。杂交受体在细胞-细胞融合试验中显示保守的ENV-辅助受体特异性。尽管D1 D2-CD 4-CCR 5足以允许ENV介导的融合，但D1-CD 4-CCR 5和人D1/小鼠D2-CD 4-CCR 5缺乏CD 4功能和与定位于D1-CD 4的中和抗体的结合。嵌合D1 D2-CD 4与CCR 5的连接揭示了人D2-CD 4的C-末端20个残基是ENV介导的有效融合所需的。杂合受体的突变显示了形成D1-D2 CD 4结构域间接触和铰链区近端残基的残基的重要性。WT人CD 4的突变证实了形成D1-D2结构域间接触的残基和铰链区近端残基对全长受体中的CD 4活性有积极贡献。
Immunoglobulin-like domain 1 of CD4 (D1-CD4) promotes HIV infection by binding the envelope glycoprotein (ENV) and exposing its coreceptor-binding site. To study CD4-ENV-coreceptor interactions, we characterized hybrid receptors having domains 1 and 2 of CD4 (D1D2-CD4) joined to the N-terminus of chemokine receptors CCR5, CXCR4, CXCR2, and DARC. Hybrid receptors showed conserved ENV-coreceptor specificity in cell-cell fusion assays. Although D1D2-CD4-CCR5 was sufficient to permit ENV-mediated fusion, D1-CD4-CCR5 and human D1/mouse D2-CD4-CCR5 lacked CD4 function and binding to a neutralizing antibody mapped to D1-CD4. Chimeric D1D2-CD4 joined to CCR5 revealed that the C-terminal 20 residues of human D2-CD4 are required for efficient ENV-mediated fusion. Mutagenesis of hybrid receptors showed the importance of residues forming D1-D2 CD4 interdomain contacts and hinge region proximal residues. Mutagenesis of WT human CD4 confirmed that residues forming D1-D2 interdomain contacts and hinge-region proximal residues contribute positively to CD4 activity in the full-length receptor.