Cryo-EM structures of the zinc transporters ZnT3 and ZnT4 provide insights into their transport mechanisms.

IF 3.5 4区 生物学 Q1 Biochemistry, Genetics and Molecular Biology FEBS Letters Pub Date : 2024-10-30 DOI:10.1002/1873-3468.15047
Hanako Ishida, Riri Yo, Zhikuan Zhang, Toshiyuki Shimizu, Umeharu Ohto
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Abstract

Zinc transporters (ZnTs) act as H+/Zn2+ antiporters, crucial for zinc homeostasis. Brain-specific ZnT3 expressed in synaptic vesicles transports Zn2+ from the cytosol into vesicles and is essential for neurotransmission, with ZnT3 dysfunction associated with neurological disorders. Ubiquitously expressed ZnT4 localized to lysosomes facilitates the Zn2+ efflux from the cytosol to lysosomes, mitigating the cell injury risk. Despite their importance, the structures and Zn2+ transport mechanisms remain unclear. We characterized the three-dimensional structures of human ZnT3 (inward-facing) and ZnT4 (outward-facing) using cryo-electron microscopy. By combining these structures, we assessed the conformational changes that could occur within the transmembrane domain during Zn2+ transport. Our results provide a structural basis for a more comprehensive understanding of the H+/Zn2+ exchange mechanisms exhibited by ZnTs.

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锌转运体 ZnT3 和 ZnT4 的低温电子显微镜(Cryo-EM)结构有助于深入了解它们的转运机制。
锌转运体(ZnTs)作为 H+/Zn2+ 反转运体,对锌平衡至关重要。大脑特异性 ZnT3 在突触小泡中表达,将 Zn2+ 从细胞膜转运到小泡中,对神经传递至关重要,ZnT3 功能障碍与神经系统疾病有关。在溶酶体中定位的泛表达 ZnT4 可促进 Zn2+ 从细胞液流出到溶酶体,从而降低细胞损伤风险。尽管ZnT4非常重要,但其结构和Zn2+转运机制仍不清楚。我们利用冷冻电镜鉴定了人类 ZnT3(内向型)和 ZnT4(外向型)的三维结构。结合这些结构,我们评估了 Zn2+ 转运过程中跨膜结构域内可能发生的构象变化。我们的研究结果为更全面地了解 ZnTs 的 H+/Zn2+ 交换机制提供了结构基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
FEBS Letters
FEBS Letters 生物-生化与分子生物学
CiteScore
7.00
自引率
2.90%
发文量
303
审稿时长
1.0 months
期刊介绍: FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.
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