Asymmetric pendrin homodimer reveals its molecular mechanism as anion exchanger.
Asymmetric pendrin homodimer reveals its molecular mechanism as anion exchanger.
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DOI：
10.1038/s41467-023-38303-0
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发表时间：
2023-05-25
影响因子：
16.6
通讯作者：
Chen, Zhenguo
中科院分区：
文献类型：
--
作者：
Liu, Qianying;Zhang, Xiang;Huang, Hui;Chen, Yuxin;Wang, Fang;Hao, Aihua;Zhan, Wuqiang;Mao, Qiyu;Hu, Yuxia;Han, Lin;Sun, Yifang;Zhang, Meng;Liu, Zhimin;Li, Geng-Lin;Zhang, Weijia;Shu, Yilai;Sun, Lei;Chen, Zhenguo
Pendrin（SLC 26 A4）是一种阴离子交换剂，在选定的上皮细胞的顶端膜中表达。Pendrin消融导致Pendred综合征，这是一种与感音神经性听力损失、甲状腺功能减退和血压降低相关的遗传性疾病。然而，其分子结构仍然未知，限制了我们对运输结构基础的理解。在这里，我们确定了冷冻电子显微镜结构的小鼠pendrin与对称和不对称的同源二聚体构象。不对称同型二聚体由一个面向内的原聚体和另一个面向外的原聚体组成，代表同时摄取和分泌-pendrin作为电中性交换剂的独特状态。这里提出的多种构象提供了一个反向交替访问机制的阴离子交换。本文提供的结构和功能数据揭示了阴离子交换裂缝的性质，并有助于理解疾病相关变体的重要性，这将有助于阐明pendrin交换机制。Pendrin SLC 26 A4对阴离子平衡起重要作用。在这里，作者解决cryo-EM结构pendrin执行同时发生的吸收和分泌的阴离子，提供了这种阴离子交换机制的结构基础。
Pendrin (SLC26A4) is an anion exchanger expressed in the apical membranes of selected epithelia. Pendrin ablation causes Pendred syndrome, a genetic disorder associated with sensorineural hearing loss, hypothyroid goiter, and reduced blood pressure. However its molecular structure has remained unknown, limiting our understanding of the structural basis of transport. Here, we determine the cryo-electron microscopy structures of mouse pendrin with symmetric and asymmetric homodimer conformations. The asymmetric homodimer consists of one inward-facing protomer and the other outward-facing protomer, representing coincident uptake and secretion- a unique state of pendrin as an electroneutral exchanger. The multiple conformations presented here provide an inverted alternate-access mechanism for anion exchange. The structural and functional data presented here disclose the properties of an anion exchange cleft and help understand the importance of disease-associated variants, which will shed light on the pendrin exchange mechanism. Pendrin SLC26A4 plays an important role for anion balance. Here, authors resolve cryo-EM structures of pendrin performing co-incident uptake and secretion of anions, providing a structural basis of this anion exchange mechanism.
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DOI：
10.3390/diagnostics11122378
发表时间：
2021-12-17
期刊：
Diagnostics (Basel, Switzerland)
影响因子：
--
作者：
Danilchenko VY;Zytsar MV;Maslova EA;Bady-Khoo MS;Barashkov NA;Morozov IV;Bondar AA;Posukh OL
通讯作者：
Posukh OL
影响因子：
16.6
作者：
通讯作者：
--
影响因子：
15.9
作者：
Choi, Byung Yoon;Kim, Hyoung-Mi;Griffith, Andrew J.
通讯作者：
Griffith, Andrew J.
影响因子：
9.8
作者：
Azaiez H;Booth KT;Ephraim SS;Crone B;Black-Ziegelbein EA;Marini RJ;Shearer AE;Sloan-Heggen CM;Kolbe D;Casavant T;Schnieders MJ;Nishimura C;Braun T;Smith RJH
通讯作者：
Smith RJH
DOI：
10.1107/s2059798318006551
发表时间：
2018-06-01
期刊：
Acta crystallographica. Section D, Structural biology
影响因子：
--
作者：
Afonine PV;Poon BK;Read RJ;Sobolev OV;Terwilliger TC;Urzhumtsev A;Adams PD
通讯作者：
Adams PD