Comparative study of curvature sensing mediated by F-BAR and an intrinsically disordered region of FBP17

Summary Membrane curvature has emerged as an intriguing physical principle underlying biological signaling and membrane trafficking. The CIP4/FBP17/Toca-1 F-BAR subfamily is unique in the BAR family because its structurally folded F-BAR domain does not contain any hydrophobic motifs that insert into membrane. While widely assumed so, whether the banana-shaped F-BAR domain alone can sense curvature has never been experimentally demonstrated. Using a nanobar-supported lipid bilayer system, we found that the F-BAR domain of FBP17 displayed minimal curvature sensing in vitro. In comparison, an alternatively spliced intrinsically disordered region (IDR) adjacent to the F-BAR domain has the membrane curvature sensing ability greatly exceeding that of F-BAR domain alone. In living cells, the presence of the IDR delayed the recruitment of FBP17 in curvature-coupled cortical waves. Collectively, we propose that contrary to the common belief, FBP17’s curvature sensing capability largely originates from IDR, not the F-BAR domain alone.