小柯机器人

蛋白质相分离启动过氧化物酶体的生物生成
2023-05-17 10:11

加拿大蒙特利尔大学Stephen W. Michnick团队发现,蛋白质相分离启动过氧化物酶体的生物生成。2023年5月10日,《自然》杂志在线发表了这项成果。

研究人员表明,Pex13与Pex5-货物进行液-液相分离(LLPS)。Pex13和Pex5的内在无序区与核孔复合体蛋白中发现的相似。过氧化物酶体蛋白的导入取决于这些内在无序区域的芳香族残基的数量和模式,这与它们在LLPS的关联聚合物模型中作为“贴纸”的作用相一致。最后,成像荧光交叉相关光谱显示,货物进口与GFP-Pex13和GFP-Pex14在过氧化物酶体膜上的瞬时聚焦有关。Pex13和Pex14在不同的时间范围内形成焦点,这表明它们可能在Pex5-货物的不同饱和浓度下形成通道。这些发现提出了一个模型,即Pex5-货物与Pex13和Pex14的LLPS导致了瞬时的蛋白质运输通道。

研究人员表示,过氧化物酶体是进行脂肪酸和氨基酸的β-氧化的细胞器。罕见和流行的疾病都是由它们的功能障碍引起的。在致病的变异基因中,有那些需要蛋白质运输到过氧体的基因。过氧物酶体的蛋白质导入机制与叶绿体也有相似之处,其独特之处在于将折叠且巨大的、直径达10纳米的蛋白质复合物运入过氧物酶体。当前的模型推测一个由跨膜蛋白形成的大孔;然而,到目前为止,还没有观察到孔的结构。在芽殖酵母中,最小的运输机制包括膜蛋白Pex13和Pex14以及与货物蛋白结合的运输受体Pex5。

附:英文原文

Title: Peroxisome biogenesis initiated by protein phase separation

Author: Ravindran, Rini, Bacellar, Isabel O. L., Castellanos-Girouard, Xavier, Wahba, Haytham M., Zhang, Zhenghao, Omichinski, James G., Kisley, Lydia, Michnick, Stephen W.

Issue&Volume: 2023-05-10

Abstract: Peroxisomes are organelles that carry out β-oxidation of fatty acids and amino acids. Both rare and prevalent diseases are caused by their dysfunction1. Among disease-causing variant genes are those required for protein transport into peroxisomes. The peroxisomal protein import machinery, which also shares similarities with chloroplasts2, is unique in transporting folded and large, up to 10nm in diameter, protein complexes into peroxisomes3. Current models postulate a large pore formed by transmembrane proteins4; however, so far, no pore structure has been observed. In the budding yeast Saccharomyces cerevisiae, the minimum transport machinery includes the membrane proteins Pex13 and Pex14 and the cargo-protein-binding transport receptor, Pex5. Here we show that Pex13 undergoes liquid–liquid phase separation (LLPS) with Pex5–cargo. Intrinsically disordered regions in Pex13 and Pex5 resemble those found in nuclear pore complex proteins. Peroxisomal protein import depends on both the number and pattern of aromatic residues in these intrinsically disordered regions, consistent with their roles as ‘stickers’ in associative polymer models of LLPS5,6. Finally, imaging fluorescence cross-correlation spectroscopy shows that cargo import correlates with transient focusing of GFP–Pex13 and GFP–Pex14 on the peroxisome membrane. Pex13 and Pex14 form foci in distinct time frames, suggesting that they may form channels at different saturating concentrations of Pex5–cargo. Our findings lead us to suggest a model in which LLPS of Pex5–cargo with Pex13 and Pex14 results in transient protein transport channels7.

DOI: 10.1038/s41586-023-06044-1

Source: https://www.nature.com/articles/s41586-023-06044-1

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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