Spc2 modulates substrate- and cleavage site-selection in the yeast signal peptidase complex.

IF 7.4 1区 生物学 Q1 CELL BIOLOGY
Journal of Cell Biology Pub Date : 2024-12-02 Epub Date: 2024-11-20 DOI:10.1083/jcb.202211035
Yeonji Chung, Chewon Yim, Gilberto P Pereira, Sungjoon Son, Lisbeth R Kjølbye, Lauren E Mazurkiewicz, Amy M Weeks, Friedrich Förster, Gunnar von Heijne, Paulo C T Souza, Hyun Kim
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引用次数: 0

Abstract

Secretory proteins are critically dependent on the correct processing of their signal sequence by the signal peptidase complex (SPC). This step, which is essential for the proper folding and localization of proteins in eukaryotic cells, is still not fully understood. In eukaryotes, the SPC comprises four evolutionarily conserved membrane subunits (Spc1-3 and Sec11). Here, we investigated the role of Spc2, examining SPC cleavage efficiency on various models and natural signal sequences in yeast cells depleted of or with mutations in Spc2. Our data show that discrimination between substrates and identification of the cleavage site by SPC is compromised when Spc2 is absent or mutated. Molecular dynamics simulation of the yeast SPC AlphaFold2-Multimer model indicates that membrane thinning at the center of SPC is reduced without Spc2, suggesting a molecular explanation for the altered substrate recognition properties of SPC lacking Spc2. These results provide new insights into the molecular mechanisms by which SPC governs protein biogenesis.

Spc2 调节酵母信号肽酶复合体的底物和裂解位点选择。
分泌蛋白主要依赖于信号肽酶复合体(SPC)对其信号序列的正确处理。这一步骤对于蛋白质在真核细胞中的正确折叠和定位至关重要,但人们对这一步骤仍不完全了解。在真核生物中,SPC 由四个进化保守的膜亚基(Spc1-3 和 Sec11)组成。在这里,我们研究了 Spc2 的作用,考察了在缺少 Spc2 或 Spc2 发生突变的酵母细胞中,SPC 对各种模型和天然信号序列的裂解效率。我们的数据表明,当 Spc2 缺失或突变时,SPC 对底物的分辨和对裂解位点的识别会受到影响。对酵母 SPC AlphaFold2-多聚体模型的分子动力学模拟表明,在没有 Spc2 的情况下,SPC 中心的膜变薄现象会减少,这表明缺乏 Spc2 的 SPC 底物识别特性的改变可以从分子上得到解释。这些结果为了解 SPC 管理蛋白质生物生成的分子机制提供了新的视角。
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
Journal of Cell Biology
Journal of Cell Biology 生物-细胞生物学
CiteScore
12.60
自引率
2.60%
发文量
213
审稿时长
1 months
期刊介绍: The Journal of Cell Biology (JCB) is a comprehensive journal dedicated to publishing original discoveries across all realms of cell biology. We invite papers presenting novel cellular or molecular advancements in various domains of basic cell biology, along with applied cell biology research in diverse systems such as immunology, neurobiology, metabolism, virology, developmental biology, and plant biology. We enthusiastically welcome submissions showcasing significant findings of interest to cell biologists, irrespective of the experimental approach.
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