Microscopic Identification of PIP2 Binding Sites on a Ca2+-activated Cl- Channel [chapter]

Tao Jiang
2021 Zenodo  
Membrane proteins dwell in a sea of phospholipids that not only structurally stabilize the proteins by providing a hydrophobic environment but also dynamically regulate protein function. While many cation channels are known to be regulated by the negatively charged phosphatidylinositol 4,5-bisphosphate (PIP2), relatively little is known about anion channel regulation by phosphoinositides. Using atomistic molecular dynamics simulations on Blue Waters combined with experimental patch clamp
more » ... patch clamp electrophysiology, the research team has identified several PIP2 binding sites in TMEM16A, a Cl- (chloride) channel that performs myriad physiological functions ranging from epithelial fluid secretion to regulation of electrical excitability. These PIP2 binding sites form a band at the cytosolic interface of the membrane that the team proposes constitutes a network to dynamically regulate this extensively allosterically regulated protein. The microscopic description of the PIP2–TMEM16A interactions provided by this research adds a crucial layer of information for understanding the regulation mechanisms of ion channels by specific lipids.
doi:10.5281/zenodo.4739640 fatcat:nkly42ccnjez5evotdvilmwgay