生物谷報道:來自美國德克薩斯州大學西南醫(yī)學中心的一個全華人研究組給出了MthK門控環(huán)的晶體結(jié)構(gòu),,其分辨率達2.8埃,,并且在沒有鈣離子的情況下獲得了同樣的晶體,。文章發(fā)表在9月22日的Cell上,。這個研究組的負責人是蔣佑興(Youxing Jiang),,文章的作者還包括葉勝(Sheng Ye),、李洋(Yang Li)和陳麗萍(Liping Chen),。
原核生物中鈣門控型K離子通道MthK,類似于真核細胞生物中的配體門控型K離子通道,,MthK能夠?qū)⑴c之結(jié)合的配基的化學能量轉(zhuǎn)化成通道開啟的機械力,。發(fā)現(xiàn)在通道上有八個配基結(jié)合結(jié)構(gòu)域(RCK結(jié)構(gòu)域),形成八聚合體門控環(huán),,鈣離子與這個門控環(huán)相結(jié)合,,從而調(diào)節(jié)了離子通道的構(gòu)象,使K離子能夠透過,。作者提供了Mthk門控環(huán)在關(guān)閉和部分開放狀態(tài)下的晶體結(jié)構(gòu)科,,同時也獲得了沒有鈣激活狀態(tài)下的門控環(huán)。進一步證實,,在電生理和生物化學等條件下,,MthK能受到鈣離子和pH值的調(diào)節(jié) 。鈣離子通過改變門控環(huán)的關(guān)閉和開啟平衡來調(diào)節(jié)該通道,,而pH則是調(diào)節(jié)門控環(huán)的穩(wěn)定性,。研究人員表示,這些新發(fā)現(xiàn)連同之前確定出的開啟狀態(tài)的MthK結(jié)構(gòu)信息使他們得以闡明RCK調(diào)節(jié)的鉀離子通道的配基門控機制,。
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.
原始出處:
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
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Youxing Jiang簡歷
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.
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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