Molecular architecture of the human caveolin-1 complex

Authors

Porta JC Jason C , Han B Bing , Gulsevin A Alican , Chung JM Jeong Min , Peskova Y Yelena , Connolly S Sarah , Mchaourab HS Hassane S , Meiler J Jens , Karakas E Erkan , Kenworthy AK Anne K , Ohi MD Melanie D .
Science advances. 2022 05 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.