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

Di-Jing Shi1, Sheng Ye2, Xu Cao1, Rongguang Zhang2(), KeWei Wang1,3,4()

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Protein Cell ›› 2013, Vol. 4 ›› Issue (12) : 942-950. DOI: 10.1007/s13238-013-3091-0
RESEARCH ARTICLE

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

  • Di-Jing Shi1, Sheng Ye2, Xu Cao1, Rongguang Zhang2(), KeWei Wang1,3,4()
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Abstract

In all six members of TRPV channel subfamily, there is an ankyrin repeat domain (ARD) in their intracellular Ntermini. Ankyrin (ANK) repeat, a common motif with typically 33 residues in each repeat, is primarily involved in protein-protein interactions. Despite the sequence similarity among the ARDs of TRPV channels, the structure of TRPV3-ARD, however, remains unknown. Here, we report the crystal structure of TRPV3-ARD solved at 1.95 ? resolution, 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 finger 3 loop that bends over and is stabilized by a network of hydrogen bonds and hydrophobic packing, instead of being flexible as seen in known TRPV-ARD structures. Electrophysiological recordings demonstrated that mutating key residues R225, R226, Q255, and F249 of finger 3 loop altered the channel activities and pharmacology. Taken all together, our findings show that TRPV3-ARD with characteristic finger 3 loop likely plays an important role in channel function and pharmacology.

Keywords

TRPV3 / ARD / keratinocyte / 2-APB / skin

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Di-Jing Shi, Sheng Ye, Xu Cao, Rongguang Zhang, KeWei Wang. Crystal structure of the N-terminal ankyrin repeat domain of TRPV3 reveals unique conformation of finger 3 loop critical for channel function. Prot Cell, 2013, 4(12): 942‒950 https://doi.org/10.1007/s13238-013-3091-0

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