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Mchaourab Lab

Molecular architecture of the human caveolin-1 complex.

AUTHORS

Porta JC , Han B , Gulsevin A , Chung JM , Peskova Y , Connolly S , Mchaourab HS , Meiler J , Karakas E , Kenworthy AK , Ohi MD . Science Advances. 2022 May 11; 8(19). eabn7232

ABSTRACT

Membrane-sculpting proteins shape the morphology of cell membranes and facilitate remodeling in response to physiological and environmental cues. Complexes of the monotopic membrane protein caveolin function as essential curvature-generating components of caveolae, flask-shaped invaginations that sense and respond to plasma membrane tension. However, the structural basis for caveolin's membrane remodeling activity is currently unknown. Here, we show that, using cryo-electron microscopy, the human caveolin-1 complex is composed of 11 protomers organized into a tightly packed disc with a flat membrane-embedded surface. The structural insights suggest a previously unrecognized mechanism for how membrane-sculpting proteins interact with membranes and reveal how key regions of caveolin-1, including its scaffolding, oligomerization, and intramembrane domains, contribute to its function.