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首页> 外文期刊>Biochimica et biophysica acta. Biomembranes >The N-terminal amphipathic helix of Pex11p self-interacts to induce membrane remodelling during peroxisome fission
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The N-terminal amphipathic helix of Pex11p self-interacts to induce membrane remodelling during peroxisome fission

机译：Pex11p的N-末端两亲螺旋自相互作用，以诱导过氧化物裂变期间的膜重塑

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摘要

Pex11p plays a crucial role in peroxisome fission. Previously, it was shown that a conserved N-terminal amphipathic helix in Pex11p, termed Pex11-Amph, was necessary for peroxisomal fission in vivo while in vitro studies revealed that this region alone was sufficient to bring about tubulation of liposomes with a lipid consistency resembling the peroxisomal membrane. However, molecular details of how Pex11-Amph remodels the peroxisomal membrane remain unknown. Here we have combined in silico, in vitro and in vivo approaches to gain insights into the molecular mechanisms underlying Pex11-Amph activity. Using molecular dynamics simulations, we observe that Pex11-Amph peptides form linear aggregates on a model membrane. Furthermore, we identify mutations that disrupted this aggregation in silico, which also abolished the peptide's ability to remodel liposomes in vitro, establishing that Pex11p oligomerisation plays a direct role in membrane remodelling. In vivo studies revealed that these mutations resulted in a strong reduction in Pex11 protein levels, indicating that these residues are important for Pex11p function. Taken together, our data demonstrate the power of combining in silico techniques with experimental approaches to investigate the molecular mechanisms underlying Pex11p-dependent membrane remodelling.
机译：Pex11p在过氧化物裂缝中起着至关重要的作用。结果表明，Pex11-AMPH的保守N-末端两亲螺旋是体内过氧化物酶裂变所必需的，同时在体外研究表明，单独的该区域足以使脂质脂肪脂质的脂质稠度具有类似于类似的脂质稠度过氧化物血型膜。然而，PEX11-AMPH如何重塑过氧异象膜的分子细节仍然是未知的。在这里，我们在Silico中组合在体外和体内方法中，以进入Pex11-AMPH活性的分子机制的见解。使用分子动力学模拟，观察到PEX11-AMPH肽在模型膜上形成线性聚集体。此外，我们鉴定破坏硅中这种聚集的突变，这也废除了肽在体外重塑脂质体的能力，建立了Pex11p寡聚物质在膜重塑中起到直接作用。在体内研究表明，这些突变导致PEX11蛋白水平的强烈降低，表明这些残留物对于PEX11P功能很重要。我们的数据一起展示了用实验方法展示在硅技术上结合的力量，以研究依赖于Pex11p依赖性膜重塑的分子机制。

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