PT  - JOURNAL ARTICLE
AU  - Lizhen Xu
AU  - Xiao Liang
AU  - Wenxuan Zhen
AU  - Zhangzhi Xue
AU  - Fangfei Zhang
AU  - Xiao Yi
AU  - Xiaoying Chen
AU  - Lidan Hu
AU  - Bei Li
AU  - Bing Zhang
AU  - Yuhang Wang
AU  - Zhenfeng Deng
AU  - Wei Yang
AU  - Han Wen
AU  - Tiannan Guo
AU  - Yi Zhu
AU  - Fan Yang
TI  - A common mechanism of temperature-sensing in thermoTRP channels
AID  - 10.1101/2022.05.23.493163
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.05.23.493163
4099  - http://biorxiv.org/content/early/2022/05/24/2022.05.23.493163.short
4100  - http://biorxiv.org/content/early/2022/05/24/2022.05.23.493163.full
AB  - Detecting temperature is crucial for the survival of living organisms. Though the thermo transient receptor potential (thermoTRP) channels, such as TRPV1 or TRPM8, have been identified as prototypic heat or cold sensors, respectively, how they detect temperature remains elusive. Here we first identified groups of clustered residues in these channels that undergo burial/exposure conformational rearrangements during temperature activation by analyzing available protein structures or hydroxyl radical footprinting-mass spectroscopy (HRF-MS). By systematically perturbing water-protein interactions at these residues, we found that the temperature sensitivity in these channels were modulated in accordance with the sidechain hydrophobicity. The changes in energy associated with changes in water-protein interactions were sufficient for thermo activation. Therefore, our study has established that the water-protein interactions as a common mechanism underlying temperature sensing in TRPM8 and TRPV1.Competing Interest StatementThe authors have declared no competing interest.