Structure of the Ancient TRPY1 Channel from Saccharomyces Cerevisiae Reveals Mechanisms of Modulation by Lipids and Calcium

Overview

Journal Structure

Publisher Cell Press

Specialties Biochemistry
Biotechnology
Cell Biology
Molecular Biology

Date 2021 Aug 28

PMID 34453887

Citations 8

Authors

Tofayel Ahmed

Collin R Nisler

Edwin C Fluck 3rd

Sanket Walujkar

Marcos Sotomayor

Vera Y Moiseenkova-Bell

Affiliations

Soon will be listed here.

Abstract

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 Å 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 Ca-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 Ca, and the molecular evolution of TRP channels.

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