Peroxisome biogenesis initiated by protein phase separation.
Peroxisome biogenesis initiated by protein phase separation.
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DOI：
10.1038/s41586-023-06044-1
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发表时间：
2023-05
期刊：
影响因子：
64.8
通讯作者：
Michnick, Stephen W. W.
中科院分区：
文献类型：
--
作者：
Ravindran, Rini;Bacellar, Isabel O. L.;Castellanos-Girouard, Xavier;Wahba, Haytham M. M.;Zhang, Zhenghao;Omichinski, James G. G.;Kisley, Lydia;Michnick, Stephen W. W.
过氧化物酶体是进行脂肪酸和氨基酸β氧化的细胞器。罕见疾病和流行疾病都是由它们的功能失调引起的。在致病变异基因中，有一些是蛋白质转运到过氧化物酶体所必需的。过氧化物酶体蛋白质进口机制与叶绿体相似，在将折叠的、直径达10纳米的蛋白质复合物运输到过氧化物酶体中是独一无二的。目前的模型假设一个由跨膜蛋白形成的大孔；然而，到目前为止，还没有观察到孔隙结构。在出芽酵母中，最小的运输机制包括膜蛋白Pex13和Pex14以及货物蛋白结合运输受体Pex5。在这里，我们证明了Pex13与Pex5-cargo进行了液-液相分离（LLPS）。Pex13和Pex5的内在无序区域类似于核孔复合物蛋白。过氧化物酶体蛋白的输入取决于这些内在无序区域中芳香残基的数量和模式，这与它们在LLPS的结合聚合物模型中作为“贴纸”的作用一致。最后，成像荧光互相关光谱显示，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在不同的时间框架内形成病灶，表明它们可能在不同的pex5 -货物饱和浓度下形成通道。我们的研究结果使我们提出了一个模型，在该模型中，pex5 -货物与Pex13和Pex14的LLPS导致瞬时蛋白质运输通道。
Peroxisomes are organelles that carry out β-oxidation of fatty acids and amino acids. Both rare and prevalent diseases are caused by their dysfunction. Among disease-causing variant genes are those required for protein transport into peroxisomes. The peroxisomal protein import machinery, which also shares similarities with chloroplasts, is unique in transporting folded and large, up to 10 nm in diameter, protein complexes into peroxisomes. Current models postulate a large pore formed by transmembrane proteins; 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 LLPS. 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 channels.
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DOI：
10.1083/jcb.144.6.1151
发表时间：
1999-03-22
期刊：
The Journal of cell biology
影响因子：
--
作者：
Girzalsky W;Rehling P;Stein K;Kipper J;Blank L;Kunau WH;Erdmann R
通讯作者：
Erdmann R
影响因子：
7.4
作者：
Cooper, Justin T.;Harris, Joel M.
通讯作者：
Harris, Joel M.
影响因子：
64.5
作者：
Albertini, M;Rehling, P;Kunau, WH
通讯作者：
Kunau, WH
影响因子：
56.9
作者：
Frey, Steffen;Richter, Ralf P.;Goerlich, Dirk
通讯作者：
Goerlich, Dirk
影响因子：
5.5
作者：
Gaussmann S;Gopalswamy M;Eberhardt M;Reuter M;Zou P;Schliebs W;Erdmann R;Sattler M
通讯作者：
Sattler M