PDF(Pubmed)
Abstract：
The CALHM proteins constitute a family of large pore channels that contains six closely related paralogs in humans. Two family members, CALHM1 and 3, have been associated with the release of ATP during taste sensation. Both proteins form heteromeric channels that activate at positive potential and decreased extracellular Ca2+ concentration. Although the structures of several family members displayed large oligomeric organizations of different size, their function has in most cases remained elusive. Our previous study has identified the paralogs CALHM2, 4 and, 6 to be highly expressed in the placenta and defined their structural properties as membrane proteins exhibiting features of large pore channels with unknown activation properties (Drożdżyk et al., 2020). Here, we investigated whether these placental paralogs would form heteromers and characterized heteromeric complexes consisting of CALHM2 and CALHM4 subunits using specific binders as fiducial markers. Both proteins assemble with different stoichiometries with the largest population containing CALHM2 as the predominant component. In these oligomers, the subunits segregate and reside in their preferred conformation found in homomeric channels. Our study has thus revealed the properties that govern the formation of CALHM heteromers in a process of potential relevance in a cellular context.
摘要：
CALHM蛋白构成大孔通道家族,其在人类中包含六个密切相关的旁系同源物。两个家庭成员,CALHM1和3与味觉过程中ATP的释放有关。两种蛋白质都形成异聚通道，在正电位下激活并降低细胞外Ca2浓度。尽管几个家庭成员的结构显示出不同大小的大型寡聚体组织，它们的功能在大多数情况下仍然难以捉摸。我们以前的研究已经确定了CALHM2，4和，6在胎盘中高度表达，并将其结构特性定义为表现出具有未知激活特性的大孔通道特征的膜蛋白（Drod各种各样。,2020）。这里,我们研究了这些胎盘旁系同源物是否会形成异聚体，并使用特异性结合剂作为基准标记物表征了由CALHM2和CALHM4亚基组成的异聚体复合物。两种蛋白质都以不同的化学计量组装，其中最大的群体含有CALHM2作为主要成分。在这些低聚物中，亚基分离并驻留在同聚体通道中的首选构象中。因此，我们的研究揭示了在细胞环境中潜在相关过程中控制CALHM异聚体形成的特性。
