An intermolecular hydrogen bonded network in the PRELID-TRIAP protein family plays a role in lipid sensing.
An intermolecular hydrogen bonded network in the PRELID-TRIAP protein family plays a role in lipid sensing.
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DOI：
10.1016/j.bbapap.2022.140867
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发表时间：
2022-10
期刊：
影响因子：
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通讯作者：
X. Miliara;T. Tatsuta;Akinori Eiyama;T. Langer;S. Rouse;Steve Matthews
中科院分区：
文献类型：
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作者：
X. Miliara;T. Tatsuta;Akinori Eiyama;T. Langer;S. Rouse;Steve Matthews
PRELID-TRIAP1家族蛋白负责线粒体中的脂质转移。载脂蛋白和脂质底物结合形式的多种结构已经被分解，使我们能够开始拼凑整个脂质转移周期的分子水平细节。在这里，我们使用分子动力学模拟来证明脂质结合是由一个扩展的、水介导的氢键网络介导的。一个关键的突变R53E被发现破坏了这个网络，导致脂质从复合体中释放出来。R53E的x射线晶体结构处于完全闭合和载子态。脂质转移分析和分子模拟使我们能够在生物学作用的背景下解释观察到的构象。总之，我们的工作提供了进一步了解线粒体中PRELID-TRIAP1对脂质转运的机制控制。
The PRELID-TRIAP1 family of proteins is responsible for lipid transfer in mitochondria. Multiple structures have been resolved of apo and lipid substrate bound forms, allowing us to begin to piece together the molecular level details of the full lipid transfer cycle. Here, we used molecular dynamics simulations to demonstrate that the lipid binding is mediated by an extended, water-mediated hydrogen bonding network. A key mutation, R53E, was found to disrupt this network, causing lipid to be released from the complex. The X-ray crystal structure of R53E was captured in a fully closed and apo state. Lipid transfer assays and molecular simulations allow us to interpret the observed conformation in the context of the biological role. Together, our work provides further understanding of the mechanistic control of lipid transport by PRELID-TRIAP1 in mitochondria.