The stepwise mechanism of TRPV6 channel blockade by polyamine spermine
Researchers from IBCh RAS, as part of an international collaboration, have elucidated how the endogenous polyamine spermine blocks the calcium-selective TRPV6 ion channel, which is hyperactive in prostate, breast, and pancreatic cancers. Using a combination of cryo-EM, molecular modeling, electrophysiology, and site-directed mutagenesis, it was shown that spermine enters the open TRPV6 pore in a stepwise manner and physically occludes it like a “plug”. These findings advance our understanding of calcium homeostasis regulation under both physiological conditions and in cancer. The study was supported by the Russian Ministry of Science and Higher Education (computational modeling) and published in Nature Communications. Learn more
3 июня