Fig. 9: Model for the role of Cavin1 DR domains in LLPS and caveola formation.
a Structural model of a Cavin1 homotrimeric assembly. The trimeric HR1 coiled-coil domain is derived from the crystal structure of the mouse Cavin1 HR1 domain11, the UC1 and HR2 domains are modelled as described previously10, and the DR domains are modelled as random coil structures (see “Methods” section for further details). The structure is shown in ribbon diagram (top) and with an electrostatic surface representation (bottom). b Proposed orientation of Cavin1 proteins on the membrane surface, with membrane-binding HR1 and HR2 domains associated with the phospholipid bilayer and negatively charged DR sequences directed outwards due to electrostatic repulsion. c Potential role of Cavin1 disordered sequences in membrane curvature generation due to steric crowding. This concept is largely derived from previous studies of other membrane-associated proteins73,74. d Potential role of Cavin1 fuzzy interactions and LLPS in membrane curvature generation, CAV1 interaction and caveola formation.
