Structural highlights
Function
[YVC1_YEAST] Required for release of calcium ions from the vacuole in response to hyperosmotic shock.[1] [2]
Publication Abstract from PubMed
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 A 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(2+)-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(2+), and the molecular evolution of TRP channels.
Structure of the ancient TRPY1 channel from Saccharomyces cerevisiae reveals mechanisms of modulation by lipids and calcium.,Ahmed T, Nisler CR, Fluck EC 3rd, Walujkar S, Sotomayor M, Moiseenkova-Bell VY Structure. 2021 Aug 24. pii: S0969-2126(21)00298-7. doi:, 10.1016/j.str.2021.08.003. PMID:34453887[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Palmer CP, Zhou XL, Lin J, Loukin SH, Kung C, Saimi Y. A TRP homolog in Saccharomyces cerevisiae forms an intracellular Ca(2+)-permeable channel in the yeast vacuolar membrane. Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):7801-5. doi: 10.1073/pnas.141036198. , Epub 2001 Jun 26. PMID:11427713 doi:http://dx.doi.org/10.1073/pnas.141036198
- ↑ Denis V, Cyert MS. Internal Ca(2+) release in yeast is triggered by hypertonic shock and mediated by a TRP channel homologue. J Cell Biol. 2002 Jan 7;156(1):29-34. Epub 2002 Jan 7. PMID:11781332 doi:http://dx.doi.org/10.1083/jcb.200111004
- ↑ Ahmed T, Nisler CR, Fluck EC 3rd, Walujkar S, Sotomayor M, Moiseenkova-Bell VY. Structure of the ancient TRPY1 channel from Saccharomyces cerevisiae reveals mechanisms of modulation by lipids and calcium. Structure. 2021 Aug 24. pii: S0969-2126(21)00298-7. doi:, 10.1016/j.str.2021.08.003. PMID:34453887 doi:http://dx.doi.org/10.1016/j.str.2021.08.003
