State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Int J Mol Sci. 2022 Apr 21;23(9):4608. doi: 10.3390/ijms23094608.
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.
线粒体肉碱/酰基辅酶 A 载体（CAC）在跨线粒体内膜转运短链、中链和长链酰基辅酶 A 时，以肉碱作为交换。然而，CAC 如何识别具有各种脂肪酸酰基的底物，特别是长链脂肪酸酰基，目前仍不清楚。在这里，我们使用核磁共振（NMR）技术表明，重组成胶束系统的 CAC 蛋白表现出线粒体载体家族的典型六跨膜结构。不同酰基辅酶 A 的化学位移扰动模式表明，CAC 中的 A76-G81 片段特异性地响应长链脂肪酰基辅酶 A。棕榈酰-L-肉碱在 CAC 通道内的分子动力学（MD）模拟显示了长链酰基辅酶 A 在胞质开放态和基质开放态下在 CAC 中的相互作用和运动。我们的数据为 CAC 的结构和转运机制提供了基于分子的理解。
