Department of Biochemistry, Duke University School of Medicine, Durham, United States.
Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, United States.
Elife. 2019 May 15;8:e45779. doi: 10.7554/eLife.45779.
The Transient Receptor Potential Vanilloid 2 (TRPV2) channel is a member of the temperature-sensing thermoTRPV family. Recent advances in cryo-electronmicroscopy (cryo-EM) and X-ray crystallography have provided many important insights into the gating mechanisms of thermoTRPV channels. Interestingly, crystallographic studies of ligand-dependent TRPV2 gating have shown that the TRPV2 channel adopts two-fold symmetric arrangements during the gating cycle. However, it was unclear if crystal packing forces played a role in stabilizing the two-fold symmetric arrangement of the channel. Here, we employ cryo-EM to elucidate the structure of full-length rabbit TRPV2 in complex with the agonist resiniferatoxin (RTx) in nanodiscs and amphipol. We show that RTx induces two-fold symmetric conformations of TRPV2 in both environments. However, the two-fold symmetry is more pronounced in the native-like lipid environment of the nanodiscs. Our data offers insights into a gating pathway in TRPV2 involving symmetry transitions.
瞬时受体电位香草素 2（TRPV2）通道是温度感应热 TRP 家族的成员。低温电子显微镜（cryo-EM）和 X 射线晶体学的最新进展为热 TRP 通道的门控机制提供了许多重要的见解。有趣的是，配体依赖性 TRPV2 门控的晶体学研究表明，在门控循环中 TRPV2 通道采用二倍对称排列。然而，尚不清楚晶体包装力是否在稳定通道的二倍对称排列中发挥作用。在这里，我们使用 cryo-EM 阐明了在纳米盘和 Amphipol 中与激动剂树脂毒素（RTx）结合的全长兔 TRPV2 的结构。我们表明 RTx 在这两种环境中诱导 TRPV2 的二倍对称构象。然而，在类似天然的纳米盘脂质环境中，二倍对称性更为明显。我们的数据为 TRPV2 中的门控途径提供了有关对称转换的见解。
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