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首页> 外文期刊>Biochemistry >Preparation,Functional Characterization,and NMR Studies of Human KCNE1,a Voltage-Gated Potassium Channel Accessory Subunit Associated with Deafness and Long QT Syndrome
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Preparation,Functional Characterization,and NMR Studies of Human KCNE1,a Voltage-Gated Potassium Channel Accessory Subunit Associated with Deafness and Long QT Syndrome

机译：人KCNE1的制备，功能表征和NMR研究，与耳聋和长QT综合征相关的电压门控钾通道次核酸亚基

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摘要

KCNE1,also known as minK,is a member of the KCNE family of membrane proteins that modulate the function of KCNQ1 and certain other voltage-gated potassium channels(K_v).Mutations in human KCNE1 cause congenital deafness and congenital long QT syndrome,an inherited predisposition to potentially life-threatening cardiac arrhythmias.Although its modulation of KCNQ1 function has been extensively characterized,many questions remain regarding KCNEl's structure and location within the channel complex.In this study,KCNE1 was overexpressed in Escherichia coli and purified.Micellar solutions of the protein were then microinjected into Xenopus oocytes expressing KCNQ1 channels,followed by electrophysiological recordings aimed at testing whether recombinant KCNE1 can co-assemble with the channel.Nativelike modulation of channel properties was observed following injection of KCNE1 in lyso-myristoylphosphatidylglycerol(LMPG)micelles,indicating that KCNE1 is not irreversibly misfolded and that LMPG is able to act as a vehicle for delivering membrane proteins into the membranes of viable cells.~1H-~(15)N TROSY NMR experiments indicated that LMPG micelles are well-suited for structural studies of KCNE1,leading to assignment of its backbone resonances and to relaxation studies.The chemical shift data confirmed that KCNEl's secondary structure includes several alpha-helices and demonstrated that its distal C-terminus is disordered.Surprisingly,for KCNE1 in LMPG micelles,there appears to be a break in alpha-helicity at sites 59-61,near the middle of the transmembrane segment,a feature that is accompanied by increased local backbone mobility.Given that this segment overlaps with sites 57-59,which are known to play a critical role in modulating KCNQ1 channel activation kinetics,this unusual structural feature likely has considerable functional relevance.
机译：kcne1，也称为貂皮，是kcne膜蛋白的成员，其调节Kcnq1的功能和某些其他电压门控钾通道（K_V）。人类Kcne1中的逆转，引起先天性耳聋和先天性长QT综合征，一种遗传易受危及生命的心律失常的易感性。虽然其对KCNQ1功能的调制得到了广泛的表征，但许多问题仍然存在关于Kcnel的结构和位置在频道复合体内的位置。本研究中，KCNE1在大肠杆菌中过表达和纯化。然后将蛋白质微内注射到表达KCNQ1通道的外爪卵卵卵状体中，然后进行用于测试重组Kcne1是否可以与通道共组装的电生理记录。在注射Lyso-Myristoylphosphosityl甘油（LMPG）胶束后，观察到通道特性的不可脂肪调制。 kcne1并不是不可逆转的错误，并且lmpg我s作为用于将膜蛋白递送到活细胞膜中的载体。〜1H-〜（15）N TroSy NMR实验表明，LMPG胶束非常适合KCNE1的结构研究，从而分配其骨干共振和放松研究。化学换档数据证实，Kcnel的二级结构包括几种α-螺旋，并证明其远端C-末端是无序的。对于LMPG胶束的KcNe1，位于脑螺旋中，似乎是α-螺旋的症状59-61，靠近跨膜段的中间，一个功能伴随着局部骨干机会增加的特征。该段与站点57-59重叠，这已知在调制KCNQ1通道激活动力学中发挥关键作用，这不寻常的结构特征可能具有相当多的功能相关性。

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  • 来源
    《Biochemistry》 |2007年第41期|共14页
  • 作者

    Changlin Tian; Carlos G.Vanoye; Congbao Kang;

  • 作者单位

    Department of Biochemistry Center for Structural Biology Department of Medicine and Department of Pharmacology Vanderbilt University School of Medicine Nashville Tennessee 37232-8725;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物化学;
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