NMR Characterization of Long-Chain Fatty Acylcarnitine Binding to the Mitochondrial Carnitine/Acylcarnitine Carrier
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作者
Zhang, Ningning; Jia, Xiaopu; Fan, Shuai; Wu, Bin; Wang, Shuqing; OuYang, Bo
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刊物名称
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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年、卷、文献号
2022, 23,
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关键词
Zhang, Ningning; Jia, Xiaopu; Fan, Shuai; Wu, Bin; Wang, Shuqing; OuYang, Bo
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摘要
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.
