Abstract
Caveolins form complexes of various sizes that deform membranes into polyhedral shapes. However, the recent structure of the 8S complex was disk-like with a flat membrane-binding surface. How can a flat complex deform membranes into nonplanar structures? Molecular dynamics simulations revealed that the 8S complex rapidly takes the form of a suction cup. Simulations on implicit membrane vesicles determined that binding is stronger when E140 gets protonated. In that case, the complex binds much more strongly to 5- and 10-nm-radius vesicles. A concave membrane-binding surface readily explains the membrane-deforming ability of caveolins by direct scaffolding. We propose that the 8S complex sits at the vertices of the caveolar polyhedra, rather than at the center of the polyhedral faces.