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...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.展开更多
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).
文摘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.
