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| Status |
Public on Jun 28, 2024 |
| Title |
Molecular Insights into the Inhibition of Proton-Activated Chloride Channel by Transfer RNA |
| Organisms |
Spodoptera frugiperda; Homo sapiens |
| Experiment type |
Other
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| Summary |
The proton-activated chloride (PAC) channel (also known as acid-sensitive outwardly rectifying anion channel, ASOR) plays a critical role in acid-induced cell death and endocytosis. However, little is known about the regulatory factors and binding partners of PAC. In this study, we discovered that transfer RNA (tRNA) interacts directly with PAC as an unexpected binding partner. Using cryo-electron microscopy, we determined that two PAC trimers and one co-purified tRNA molecule form a stable complex via a highly conserved KR motif, representing the closed conformation. tRNA is located on the intracellular side of PAC, blocking the channel pores. Furthermore, electrophysiological data showed that tRNA modulates chloride currents and channel open probability of PAC, thus protecting against acid-induced cell death. Our study provides insight into the regulation of PAC activity by cytosolic tRNA and extends the role of tRNAs in pathological and physiological events.
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| Overall design |
RNA profiles of the RNAs co-purified with Xenopus tropicalis PAC (xPAC) and Homo sapiens PAC (hPAC), respectively.
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| Web link |
https://www.nature.com/articles/s41422-024-00993-6
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| Contributor(s) |
Chi P, Wang X, Li J, Yang H, Li K, Zhang Y, Lin S, Yu L, Liu S, Chen L, Ren R, Wu J, Huang Z, Geng J, Deng D |
| Citation(s) |
38942816 |
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| Submission date |
Oct 26, 2022 |
| Last update date |
Jun 29, 2024 |
| Contact name |
pengliang chi |
| E-mail(s) |
chipengliang@stu.scu.edu.cn
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| Phone |
18428359657
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| Organization name |
Sichuan University
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| Street address |
No.17 People's South Road
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| City |
Chengdu |
| State/province |
Sichuan province |
| ZIP/Postal code |
610041 |
| Country |
China |
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| Platforms (2) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL27985 |
Illumina NextSeq 500 (Spodoptera frugiperda) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA896180 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE216637_RAW.tar |
60.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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