Two cooperative binding sites sensitize PI(4,5)P₂ recognition by the tubby domain.

ABSTRACT: Phosphoinositides (PIs) are lipid signaling molecules that operate by recruiting proteins to cellular membranes via PI recognition domains. The dominant PI of the plasma membrane is phosphatidylinositol 4,5-bisphosphate [PI(4,5)P₂]. One of only two PI(4,5)P₂ recognition domains characterized in detail is the tubby domain. It is essential for targeting proteins into cilia involving reversible membrane association. However, the PI(4,5)P₂ binding properties of tubby domains have remained enigmatic. Here, we used coarse-grained molecular dynamics simulations to explore PI(4,5)P₂ binding by the prototypic tubby domain. The comparatively low PI(4,5)P₂ affinity of the previously described canonical binding site is underpinned in a cooperative

SUBMITTER: Thallmair V 

PROVIDER: S-EPMC9451155 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature