Binding of Ca²⁺-independent C2 domains to lipid membranes: A multi-scale molecular dynamics study.

ABSTRACT: C2 domains facilitate protein interactions with lipid bilayers in either a Ca²⁺-dependent or -independent manner. We used molecular dynamics (MD) simulations to explore six Ca²⁺-independent C2 domains, from KIBRA, PI3KC2α, RIM2, PTEN, SHIP2, and Smurf2. In coarse-grained MD simulations these C2 domains formed transient interactions with zwitterionic bilayers, compared with longer-lived interactions with anionic bilayers containing phosphatidylinositol bisphosphate (PIP₂). Type I C2 domains bound non-canonically via the front, back, or side of the β sandwich, whereas type II C2 domains bound canonically, via the top loops. C2 domains interacted strongly with membranes containing PIP₂, causing bound anionic lipids to cluster around the protein. Bin

SUBMITTER: Larsen AH 

PROVIDER: S-EPMC8507603 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature