Caveolin assemblies displace one bilayer leaflet to organize and bend membranes.

Caveolae are membrane invaginations heavily implicated in cellular physiology and disease; however, how their unique shape and function are produced remains enigmatic. Here, following on recent characterization of the unusual structure of the CAV1-8S oligomer, we examine the molecular details of its interactions with its solvating lipid membrane. We describe a novel mode of membrane interaction-which we term 'leaflet replacement'-for the CAV1-8S complex that has not previously been observed for any other protein. The biophysical consequences of this unique molecular organization provide mechanistic insights into the functions and organization of caveolae in cells.