Cryo-EM structures of the TTYH family reveal a novel architecture for lipid interactions.
Cryo-EM structures of the TTYH family reveal a novel architecture for lipid interactions.
复制标题
DOI：
10.1038/s41467-021-25106-4
复制
发表时间：
2021-08-12
影响因子：
16.6
通讯作者：
Dutzler R
中科院分区：
文献类型：
--
作者：
Sukalskaia A;Straub MS;Deneka D;Sawicka M;Dutzler R
Tweety同源物（TTYH）是在脑中丰富的真核细胞膜蛋白的保守家族的成员。这三种人类旁系同源物被分配为起阴离子通道的作用，所述阴离子通道由Ca 2+或细胞肿胀激活。为了揭示它们未知的结构及其与功能的关系，我们通过冷冻电子显微镜确定了人TTYH 1 -3的结构。所有的结构都显示出含有五个跨膜片段和一个扩展的胞外结构域的二聚体膜蛋白的等同特征。由于没有一种蛋白质显示出让人联想到阴离子通道的属性，我们重新进行了功能实验，没有发现任何离子传导的迹象。相反，我们发现密度在一个扩展的疏水口袋中包含的胞外结构域出现的脂质双层，这表明TTYH蛋白在与脂质样化合物的相互作用驻留在膜中的作用。跨膜蛋白的人类Tweety同源物（TTYH）家族已被认为充当氯离子通道。在这里，作者提出了3种人类TTYH旁系同源物的冷冻电镜结构，这些结构没有显示出阴离子通道的预期特征，而是似乎与膜中的脂质样化合物相互作用;这表明参与了脂质相关过程。
The Tweety homologs (TTYHs) are members of a conserved family of eukaryotic membrane proteins that are abundant in the brain. The three human paralogs were assigned to function as anion channels that are either activated by Ca2+ or cell swelling. To uncover their unknown architecture and its relationship to function, we have determined the structures of human TTYH1–3 by cryo-electron microscopy. All structures display equivalent features of a dimeric membrane protein that contains five transmembrane segments and an extended extracellular domain. As none of the proteins shows attributes reminiscent of an anion channel, we revisited functional experiments and did not find any indication of ion conduction. Instead, we find density in an extended hydrophobic pocket contained in the extracellular domain that emerges from the lipid bilayer, which suggests a role of TTYH proteins in the interaction with lipid-like compounds residing in the membrane. The human Tweety homologue (TTYH) family of transmembrane proteins have been suggested to act as chloride channels. Here the authors present cryo-EM structures of the 3 human TTYH paralogs that do not display the expected features of an anion channel, and instead appear to interact with lipid-like compounds residing in the membrane; suggesting an involvement in lipid-associated processes.
登录
查看更多内容
影响因子：
5.6
作者：
Lee, Seok-Yong;Letts, James A.;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick
人类 GABAA 受体的晶体结构。
影响因子：
64.8
作者：
Miller PS;Aricescu AR
通讯作者：
Aricescu AR
影响因子：
14.8
作者：
Hagn F;Nasr ML;Wagner G
通讯作者：
Wagner G
DOI：
10.1085/jgp.201611650
发表时间：
2016-11
期刊：
The Journal of general physiology
影响因子：
--
作者：
Lim NK;Lam AK;Dutzler R
通讯作者：
Dutzler R
影响因子：
6
作者：
Bae, Yeonju;Kim, Ajung;Hwang, Eun Mi
通讯作者：
Hwang, Eun Mi