Lipids modulate the conformational dynamics of a secondary multidrug transporter.
Lipids modulate the conformational dynamics of a secondary multidrug transporter.
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脂质调节次级多药转运蛋白的构象动力学。
DOI：
10.1038/nsmb.3262
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发表时间：
2016-08
影响因子：
16.8
通讯作者：
Mchaourab HS
中科院分区：
文献类型：
--
作者：
Martens C;Stein RA;Masureel M;Roth A;Mishra S;Dawaliby R;Konijnenberg A;Sobott F;Govaerts C;Mchaourab HS
与脂质的直接相互作用已成为膜蛋白折叠、结构和功能的关键决定因素，但对脂质如何调节蛋白质动力学的理解仍然缺乏。在这里，我们系统地探索了脂类对来自乳酸乳球菌的质子驱动的多药转运体LmrP的构象动力学的影响，利用先前显示的自旋标签对之间的距离模式来识别蛋白质的交替进入。我们在分子水平上揭示了脂质头基团如何塑造转运体的构象能量景观。从我们的数据中出现的模型假设脂质头基团和带电残基的保守基序之间的直接相互作用，通过蛋白质内部静电相互作用的相互作用来控制构象平衡。总之，我们的数据为脂质双分子层中继发性多药转运的综合模型奠定了基础。
Direct interactions with lipids have emerged as key determinants of the folding, structure and function of membrane proteins, but an understanding of how lipids modulate protein dynamics is still lacking. Here, we systematically explored the effects of lipids on the conformational dynamics of the proton-powered, multidrug transporter LmrP from Lactococcus lactis utilizing the pattern of distances between spin label pairs previously shown to fingerprint alternating access of the protein. We uncover at the molecular level how the lipid headgroups shape the conformational energy landscape of the transporter. The model emerging from our data hypothesizes a direct interaction between lipid headgroups and a conserved motif of charged residues that control the conformational equilibrium through an interplay of electrostatic interactions within the protein. Together, our data lay the foundation for a comprehensive model of secondary multidrug transport in lipid bilayers.