Structure of a human IgA1 Fab fragment at 1.55Å resolution: potential effect of the constant domains on antigen-affinity modulation
Structure of a human IgA1 Fab fragment at 1.55Å resolution: potential effect of the constant domains on antigen-affinity modulation
复制标题
DOI：
10.1107/s0907444912048664
复制
发表时间：
2013-03-01
影响因子：
2.2
通讯作者：
Buschiazzo, Alejandro
中科院分区：
文献类型：
--
作者：
Correa, Agustin;Trajtenberg, Felipe;Buschiazzo, Alejandro
尽管是人类中最丰富的一类免疫球蛋白，并在适应性免疫应答中发挥核心作用，但仍然缺乏人同种型A抗体（IgA）的抗原结合区的高分辨率结构数据。现在报道了三种不同晶体形式的IgA 1的人Fab片段的晶体结构。其三维结构与其他Fab类相似，但FabA 1似乎更刚性，受到重链可变区和恒定区（VHCH 1）之间界面中的疏水核心以及连接轻链和重链的二硫键的限制，影响相对重链/轻链方向。同样的抗体的晶体结构，但与G-同种型CH 1，据报道，显示不同的抗原亲和力也已解决。差异结构特征揭示了恒定/可变结构域远距离效应的合理机制，从而抗体类别转换可以改变抗原亲和力。
Despite being the most abundant class of immunoglobulins in humans and playing central roles in the adaptive immune response, high-resolution structural data are still lacking for the antigen-binding region of human isotype A antibodies (IgAs). The crystal structures of a human Fab fragment of IgA1 in three different crystal forms are now reported. The three-dimensional organization is similar to those of other Fab classes, but FabA1 seems to be more rigid, being constrained by a hydrophobic core in the interface between the variable and constant domains of the heavy chain (VHCH1) as well as by a disulfide bridge that connects the light and heavy chains, influencing the relative heavy/light-chain orientation. The crystal structure of the same antibody but with a G-isotype CH1 which is reported to display different antigen affinity has also been solved. The differential structural features reveal plausible mechanisms for constant/variable-domain long-distance effects whereby antibody class switching could alter antigen affinity.