Transient receptor potential canonical 3 (TRPC3) channel belongs to the superfamily of transient receptor potential (TRP) channels which mediate Ca2+ influx into the cell. These channels constitute essential elements of cellular signalling. TRPC3 is primarily gated by lipids, and its surface expression has been shown to be dependent on cholesterol, yet a comprehensive exploration of its interaction with this lipid has thus far not emerged. Here, through 80 µs of coarse-grained molecular dynamics simulations, we show that cholesterol interacts with multiple elements of the transmembrane machinery of TRPC3. Through our approach, we identify an annular binding site for cholesterol on the pre-S1 helix, and a non-annular site at the interface between the voltage-sensor like domain and pore domains. Here cholesterol interacts with exposed polar residues, and possibly acts to stabilise the domain interface. p { margin-bottom: 0.08in; color: #000000; line-height: 0.24in; text-align: justify; orphans: 2; widows: 2; background: transparent }p.western { font-family: "Palatino Linotype", serif; font-size: 12pt }p.cjk { font-family: "Palatino Linotype", serif; font-size: 12pt; so-language: de-DE }p.ctl { font-family: "Palatino Linotype", serif }a:visited { color: #954f72; text-decoration: underline }a:link { color: #0000ff; text-decoration: underline }

{"references": ["Clarke, A et al (2022) Exploring TRPC3 Interaction with Cholesterol through Coarse-Grained Molecular Dynamics Simulations"]}