对哺乳动物 VMAT2 进行冷冻电镜分析会导致蛋白质折叠不规范

IF 14.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2024-08-02 DOI:10.1038/s41467-024-50934-5

Ying Lyu, Chunting Fu, Haiyun Ma, Zhaoming Su, Ziyi Sun, Xiaoming Zhou

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引用次数: 0

摘要

囊泡单胺转运体 2（Vesicular monoamine transporter 2，VMAT2）属于主要促进剂超家族（major facilitator superfamily，MFS），介导细胞质中的单胺包装成突触前囊泡。在这里，我们展示了两种 VMAT2 的低温电子显微镜结构，其中一种青蛙 VMAT2 采用了典型的 MFS 折叠结构，而另一种经过改造的绵羊 VMAT2 则采用了非典型折叠结构。这两种 VMAT2 蛋白都能介导细胞吸收选择性荧光 VMAT2 底物。分子对接、底物结合和运输分析揭示了 VMAT2 潜在的底物结合机制。同时，在解释工程膜蛋白结构时应谨慎。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Engineering of a mammalian VMAT2 for cryo-EM analysis results in non-canonical protein folding

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Engineering of a mammalian VMAT2 for cryo-EM analysis results in non-canonical protein folding

Vesicular monoamine transporter 2 (VMAT2) belongs to the major facilitator superfamily (MFS), and mediates cytoplasmic monoamine packaging into presynaptic vesicles. Here, we present two cryo-EM structures of VMAT2, with a frog VMAT2 adopting a canonical MFS fold and an engineered sheep VMAT2 adopting a non-canonical fold. Both VMAT2 proteins mediate uptake of a selective fluorescent VMAT2 substrate into cells. Molecular docking, substrate binding and transport analysis reveal potential substrate binding mechanism in VMAT2. Meanwhile, caution is advised when interpreting engineered membrane protein structures.

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.