U-shaped caveolin-1 conformations are tightly regulated by hydrogen bonds with lipids: U-shaped Caveolin-1 Conformations are Tightly Regulated by Hydrogen Bonds with Lipids

: The structure and dynamics of a truncated (residues 82-136) caveolin-1 (Cav1) construct having a helix-break-helix motif are explored by both all-atom free energy and molecular dynamics (MD) simulations in an explicit bilayer membrane. Two stable Cav1 conformations with small (LB-Cav1) and large hinge angles (RB-Cav1) between two helices are identified although their relative free energy cannot be reliably estimated due to the sampling issues. RB-Cav1s contain one or two lipids residing between the helices that are hydrogen bonded (h-bonded) to both helices in a multidentate fashion. LB-Cav1s show the helices with mono-dentate lipid h-bond interactions or multidentate interactions limited to a single helix at most. The two conformational states of Cav1 remain their initial state during 2-μs MD simulation, suggesting that there is a significant hidden barrier (other than the insertion depth of Cav1 and its hinge angle) and the Cav1 conformational states are tightly regulated by the h-bonds between Cav1 and lipids along with the associated lipid rearrangement during the course of Cav1 conformational changes. © 2019 Wiley Periodicals, Inc.