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首页> 外文期刊>Biochemistry >Magic Angle Spinning Nuclear Magnetic Resonance Characterization of Voltage-Dependent Anion Channel Gating in Two-Dimensional Lipid Crystalline Bilayers
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Magic Angle Spinning Nuclear Magnetic Resonance Characterization of Voltage-Dependent Anion Channel Gating in Two-Dimensional Lipid Crystalline Bilayers

机译：二维脂质晶体双层电压依赖性阴离子通道旋转核磁共振旋转核磁共振特征

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摘要

The N-terminus of the voltage-dependent anion channel (VDAC) has been proposed to contain the mechanistically important gating helices that modulate channel opening and closing. In this study, we utilize magic angle spinning nuclear magnetic resonance (MAS NMR) to determine the location and structure of the N-terminus for functional channels in lipid bilayers by measuring long-range C-13-C-13 distances between residues in the N-terminus and other domains of VDAC reconstituted into DMPC lipid bilayers. Our structural studies show that the distance between A14 C-beta in the N-terminal helix and S193 C beta is similar to 4-6 angstrom. Furthermore, VDAC phosphorylation by a mitochondrial kinase at residue S193 has been claimed to delay mitochondrial cell death by causing a conformational change that closes the channel, and a VDAC-Ser193Glu mutant has been reported to show properties very similar to those of phosphorylated VDAC in a cellular context. We expressed VDAC-S193E and reconstituted it into DMPC lipid bilayers. Two-dimensional C-13-C-13 correlation experiments showed chemical shift perturbations for residues located in the N-terminus, indicating possible structural perturbations to that region. However, electrophysiological data recorded on VDAC-S193E showed that channel characteristics were identical to those of wild type samples, indicating that phosphorylation of S193 does not directly affect channel gating. The combination of NMR and electrophysiological results allows us to discuss the validity of proposed gating models.
机译：已经提出了电压依赖性阴离子通道（VDAC）的N-末端以包含调制通道开启和关闭的机械方式重要的门控螺旋。在这项研究中，我们利用魔法角度旋转核磁共振（MAS NMR）来确定通过测量残留物之间的残留物之间的远程C-13-C-13距离来确定脂质双层的功能通道的N-末端的位置和结构N-末端和其他VDAC结构域重构成DMPC脂质双层。我们的结构研究表明，N末端螺旋和S193Cβ中A14 C-β之间的距离类似于4-6埃。此外，已经要求通过导致关闭通道的构象变化，延迟了残留物S193的线粒体激酶的VDAC磷酸化，并据报道，据报道了Vdac-Ser193Glu突变体显示与a中的磷酸化Vdac非常相似的性质蜂窝环境。我们表示VDAC-S193E并将其重构为DMPC脂质双层。二维C-13-C-13相关实验表明，位于N-末端的残留物的化学变化扰动，表明可能对该区域的结构扰动。然而，在VDAC-S193E上记录的电生理数据表明，信道特性与野生型样品的相同，表明S193的磷酸化不会直接影响通道门控。 NMR和电生理结果的组合使我们能够讨论所提出的门控模型的有效性。

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  • 来源
    《Biochemistry》 |2015年第4期|共12页
  • 作者

    Eddy Matthew T.; Andreas Loren; Teijido Oscar; Su Yongchao; Clark Lindsay; Noskov Sergei Y.; Wagner Gerhard; Rostovtseva Tatiana K.; Griffin Robert G.;

  • 作者单位

    MIT Dept Chem Cambridge MA 02139 USA;

    MIT Dept Chem Cambridge MA 02139 USA;

    Eunice Kennedy Shriver Natl Inst Child Hlth &

    Hum Program Phys Biol NIH Bethesda MD 20892 USA;

    MIT Dept Chem Cambridge MA 02139 USA;

    MIT Dept Chem Cambridge MA 02139 USA;

    Eunice Kennedy Shriver Natl Inst Child Hlth &

    Hum Program Phys Biol NIH Bethesda MD 20892 USA;

    Harvard Univ Sch Med Dept Mol Pharmacol &

    Biochem Boston MA 02115 USA;

    Eunice Kennedy Shriver Natl Inst Child Hlth &

    Hum Program Phys Biol NIH Bethesda MD 20892 USA;

    MIT Dept Chem Cambridge MA 02139 USA;

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  • 正文语种 eng
  • 中图分类 生物化学;
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