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Cel;:配体门控的K离子通道结构被破译

来源:本站原创 2006-10-05 23:37

生物谷报道:来自美国德克萨斯州大学西南医学中心的一个全华人研究组给出了MthK门控环的晶体结构,其分辨率达2.8埃,并且在没有钙离子的情况下获得了同样的晶体。文章发表在9月22日的Cell上。这个研究组的负责人是蒋佑兴(Youxing Jiang),文章的作者还包括叶胜(Sheng Ye)、李洋(Yang Li)和陈丽萍(Liping Chen)。

   原核生物中钙门控型K离子通道MthK,类似于真核细胞生物中的配体门控型K离子通道,MthK能够将与之结合的配基的化学能量转化成通道开启的机械力。发现在通道上有八个配基结合结构域(RCK结构域),形成八聚合体门控环,钙离子与这个门控环相结合,从而调节了离子通道的构象,使K离子能够透过。作者提供了Mthk门控环在关闭和部分开放状态下的晶体结构科,同时也获得了没有钙激活状态下的门控环。进一步证实,在电生理和生物化学等条件下,MthK能受到钙离子和pH值的调节 。钙离子通过改变门控环的关闭和开启平衡来调节该通道,而pH则是调节门控环的稳定性。研究人员表示,这些新发现连同之前确定出的开启状态的MthK结构信息使他们得以阐明RCK调节的钾离子通道的配基门控机制。

MthK is a prokaryotic Ca2+-gated K+ channel that, like other ligand-gated channels, converts the chemical energy of ligand binding to the mechanical force of channel opening. The channel's eight ligand-binding domains, the RCK domains, form an octameric gating ring in which Ca2+ binding induces conformational changes that open the channel. Here we present the crystal structures of the MthK gating ring in closed and partially open states at 2.8 Å, both obtained from the same crystal grown in the absence of Ca2+. Furthermore, our biochemical and electrophysiological analyses demonstrate that MthK is regulated by both Ca2+ and pH. Ca2+ regulates the channel by changing the equilibrium of the gating ring between closed and open states, while pH regulates channel gating by affecting gating-ring stability. Our findings, along with the previously determined open MthK structure, allow us to elucidate the ligand gating mechanism of RCK-regulated K+ channels.

原始出处:

Crystal Structures of a Ligand-free MthK Gating Ring: Insights into the Ligand Gating Mechanism of K+ Channels
Sheng Ye, Yang Li, Liping Chen, and Youxing Jiang
[Summary] [Full Text] [PDF] [Supplemental Data]

Youxing Jiang简历

Name:
  Youxing Jiang, Ph.D.
Academic Title:
  Assistant Professor
Primary Appointment:
  Physiology
School:
  Graduate School of Biomedical Sciences
Southwestern Medical School
Degree Program:
  Molecular Biophysics
Neuroscience
Department Website:
  Department of Physiology
Email:
  Youxing Jiang, Ph.D.


EDUCATION
 
  1992   Peking University
B.S. Chemistry
  1997   Yale University
Ph.D. Chemistry
 
FELLOWSHIPS
 
  1997 - 2003   Rockefeller University
Molecular Neurobiology and Biophysics
 
HONORS AND AWARDS
 
  2003   Endowed Scholar
UT Southwestern Medical Center at Dallas

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