Crystal structure of the N-terminal ankyrin repeat domain of TRPV3 reveals unique conformation of fi nger 3 loop critical for channel function  

作　　者：Di-Jing Shi Sheng Ye Xu Cao Rongguang Zhang KeWei Wang 

机构地区：[1]Department of Neurobiology,Neuroscience Research Institute,Peking University Health Science Center,Beijing 100191,China [2]National Laboratory of Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China [3]Department of Molecular and Cellular Pharmacology,State Key Laboratory of Natural and Biomimetic Drugs,Peking University School of Pharmaceutical Sciences,Beijing 100191,China [4]PKU-IDG/McGovern Institute for Brain Research,Peking University,Beijing 100871,China

出　　处：《Protein & Cell》2013年第12期942-950,共9页蛋白质与细胞（英文版）

基　　金：This work was supported by research grants from the National Natural Science Foundation of China to KWW(Grant Nos.30970919 and 81221002);the National Basic Research Program(973 Program)to KWW(No.2013CB531300).

摘　　要：In all six members of TRPV channel subfamily,there is an ankyrin repeat domain(ARD)in their intracellular N-termini.Ankyrin(ANK)repeat,a common motif with typi-cally 33 residues in each repeat,is primarily involved in protein-protein interactions.Despite the sequence similarity among the ARDs of TRPV channels,the struc-ture of TRPV3-ARD,however,remains unknown.Here,we report the crystal structure of TRPV3-ARD solved at 1.95Åresolution,which reveals six-ankyrin repeats.While overall structure of TRPV3-ARD is similar to ARDs from other members of TRPV subfamily;it,however,features a noticeable fi nger 3 loop that bends over and is stabilized by a network of hydrogen bonds and hydrophobic pack-ing,instead of being fl exible as seen in known TRPV-ARD structures.Electrophysiological recordings demonstrated that mutating key residues R225,R226,Q255,and F249 of fi nger 3 loop altered the channel activities and pharmacol-ogy.Taken all together,our findings show that TRPV3-ARD with characteristic fi nger 3 loop likely plays an im-portant role in channel function and pharmacology.

关 键 词：TRPV3 ARD KERATINOCYTE 2-APB skin 

分 类 号：R56[医药卫生—呼吸系统]