NMR Characterization of Long-Chain Fatty Acylcarnitine Binding to the Mitochondrial Carnitine/Acylcarnitine Carrier.
NMR Characterization of Long-Chain Fatty Acylcarnitine Binding to the Mitochondrial Carnitine/Acylcarnitine Carrier.
复制标题
长链脂肪酰肉碱与线粒体肉碱/酰肉碱载体结合的 NMR 表征
DOI：
10.3390/ijms23094608
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发表时间：
2022-04-21
影响因子：
5.6
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中科院分区：
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线粒体肉毒碱/酰基肉毒碱载体（CAC）转运短、中、长碳链酰基肉毒碱穿过线粒体内膜以交换肉毒碱。CAC如何识别具有各种脂肪酰基，特别是长链脂肪酰基的底物，目前尚不清楚。在这里，使用核磁共振（NMR）技术，我们已经表明，CAC蛋白重组成胶束系统表现出典型的线粒体载体家族的六个跨膜结构。不同脂肪酰基肉毒碱的化学位移微扰模式表明CAC中的A76-G81片段特异性地响应于长链脂肪酰基肉毒碱。分子动力学模拟CAC通道内的棕榈酰-L-肉毒碱，分别在胞质开放状态和基质开放状态下的CAC中的相互作用和运动。我们的数据提供了一个基于分子的理解CAC的结构和运输机制。
The mitochondrial carnitine/acylcarnitine carrier (CAC) transports short-, medium- and long-carbon chain acylcarnitines across the mitochondrial inner membrane in exchange for carnitine. How CAC recognizes the substrates with various fatty acyl groups, especially long-chain fatty acyl groups, remains unclear. Here, using nuclear magnetic resonance (NMR) technology, we have shown that the CAC protein reconstituted into a micelle system exhibits a typical six transmembrane structure of the mitochondrial carrier family. The chemical shift perturbation patterns of different fatty acylcarnitines suggested that the segment A76–G81 in CAC specifically responds to the long-chain fatty acylcarnitine. Molecular dynamics (MD) simulations of palmitoyl-L-carnitine inside the CAC channel showed the respective interaction and motion of the long-chain acylcarnitine in CAC at the cytosol-open state and matrix-open state. Our data provided a molecular-based understanding of CAC structure and transport mechanism.