Caveolae are an abundant feature of the plasma membrane of many mammalian cell 
types, and have key roles in mechano-transduction, metabolic regulation, and 
vascular permeability. Caveolin and cavin proteins, as well as EHD2 and pacsin 
2, are all present in caveolae. How these proteins assemble to form a protein 
interaction network for caveolar morphogenesis is not known. Using in vivo 
crosslinking, velocity gradient centrifugation, immuno-isolation, and tandem 
mass spectrometry, we determine that cavins and caveolins assemble into a 
homogenous 80S complex, which we term the caveolar coat complex. There are no 
further abundant components within this complex, and the complex excludes EHD2 
and pacsin 2. Cavin 1 forms trimers and interacts with caveolin 1 with a molar 
ratio of about 1∶4. Cavins 2 and 3 compete for binding sites within the overall 
coat complex, and form distinct subcomplexes with cavin 1. The core interactions 
between caveolin 1 and cavin 1 are independent of cavin 2, cavin 3, and EHD2 
expression, and the cavins themselves can still interact in the absence of 
caveolin 1. Using immuno-electron microscopy as well as a recently developed 
protein tag for electron microscopy (MiniSOG), we demonstrate that caveolar coat 
complexes form a distinct coat all around the caveolar bulb. In contrast, and 
consistent with our biochemical data, EHD2 defines a different domain at the 
caveolar neck. 3D electron tomograms of the caveolar coat, labeled using 
cavin-MiniSOG, show that the caveolar coat is composed of repeating units of a 
unitary caveolar coat complex.