CD8αβ异二聚体的结构与突变分析以及与CD8αα同二聚体的比较。
Structural and mutational analyses of a CD8alphabeta heterodimer and comparison with the CD8alphaalpha homodimer.
作者信息
Chang Hsiu-Ching, Tan Kemin, Ouyang Jing, Parisini Emilio, Liu Jin-huan, Le Yi, Wang Xiasong, Reinherz Ellis L, Wang Jia-huai
机构信息
Laboratory of Immunobiology, Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
出版信息
Immunity. 2005 Dec;23(6):661-71. doi: 10.1016/j.immuni.2005.11.002.
The crystal structure of a recombinant mouse single chain CD8alphabeta ectodomains at 2.4 A resolution reveals paired immunoglobulin variable region-like domains with a striking resemblance to CD8alphaalpha in size, shape, and surface electrostatic potential of complementarity-determining regions (CDR), despite <20% sequence identity between the CD8alpha and CD8beta subunits. Unlike the CD8alpha subunit(s) in the heterodimer or homodimer, the CDR1 loop of CD8beta tilts away from its corresponding CDR2 and CDR3 loops. Consistent with this observation, independent mutational studies reveal that alanine substitutions of residues in the CDR1 loop of CD8beta have no effect on CD8alphabeta coreceptor function, whereas mutations in CD8beta CDR2 and CDR3 loops abolish CD8alphabeta coreceptor activity. The implications of these findings and additional CD8alpha mutational studies for CD8alphabeta- versus CD8alphaalpha-MHCI binding are discussed.
分辨率为2.4埃的重组小鼠单链CD8αβ胞外域晶体结构显示，其配对的免疫球蛋白可变区样结构域在大小、形状和互补决定区（CDR）的表面静电势方面与CD8αα惊人地相似，尽管CD8α和CD8β亚基之间的序列同一性小于20%。与异二聚体或同二聚体中的CD8α亚基不同，CD8β的CDR1环向远离其相应的CDR2和CDR3环倾斜。与这一观察结果一致，独立的突变研究表明，CD8β的CDR1环中残基的丙氨酸替代对CD8αβ共受体功能没有影响，而CD8β的CDR2和CDR3环中的突变则消除了CD8αβ共受体活性。讨论了这些发现以及额外的CD8α突变研究对CD8αβ与CD8αα-MHC I结合的影响。
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