Abstract：
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.
摘要：
线粒体肉碱/酰基肉碱载体（CAC）转运短，穿过线粒体内膜的中碳链和长碳链酰基肉碱交换肉碱。CAC如何识别具有各种脂肪酰基的底物，尤其是长链脂肪酰基,尚不清楚。这里,使用核磁共振（NMR）技术，我们已经表明，重组成胶束系统的CAC蛋白表现出典型的线粒体载体家族的六个跨膜结构。不同脂肪酰基肉碱的化学位移扰动模式表明，CAC中的片段A76-G81特异性响应长链脂肪酰基肉碱。CAC通道内棕榈酰-L-肉碱的分子动力学（MD）模拟显示了CAC中长链酰基肉碱在细胞质开放状态和基质开放状态下的相互作用和运动。我们的数据提供了对CAC结构和传输机制的基于分子的理解。
