期刊
STRUCTURE
卷 30, 期 1, 页码 139-+出版社
CELL PRESS
DOI: 10.1016/j.str.2021.08.003
关键词
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资金
- National Institutes of Health [R01GM103899, R01GM129357]
- National Science Foundation through XSEDE [XRAC MCB140226, MCB190084P, PAS1037, PAA0217]
- OSU/NIH molecular biophysics training grant [T32GM118291]
The study presents the structure of the fungal TRP channel TRPY1, revealing distinctive structural folds for the N and C termini compared to other eukaryotic TRP channels. It identifies an inhibitory PI(3)P lipid-binding site and two Ca2+-binding sites, providing insights into the modulation of TRPY1 by lipids and Ca2+, as well as the evolutionary history of TRP channels.
Transient receptor potential (TRP) channels emerged in fungi as mechanosensitive osmoregulators. The Saccharomyces cerevisiae vacuolar TRP yeast 1 (TRPY1) is the most studied TRP channel from fungi, but the structure and details of channel modulation remain elusive. Here, we describe the full-length cryoelectron microscopy structure of TRPY1 at 3.1 angstrom resolution in a closed state. The structure, despite containing an evolutionarily conserved and archetypical transmembrane domain, reveals distinctive structural folds for the cytosolic N and C termini, compared with other eukaryotic TRP channels. We identify an inhibitory phosphatidylinositol 3-phosphate (PI(3)P) lipid-binding site, along with two Ca2+-binding sites: a cytosolic site, implicated in channel activation and a vacuolar lumen site, implicated in inhibition. These findings, together with data from microsecond-long molecular dynamics simulations and a model of a TRPY1 open state, provide insights into the basis of TRPY1 channel modulation by lipids and Ca2+, and the molecular evolution of TRP channels.
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