Molecular architecture of the human caveolin-1 complex.

Porta, Jason C; Han, Bing; Gulsevin, Alican; Chung, Jeong Min; Peskova, Yelena; Connolly, Sarah; Mchaourab, Hassane S; Meiler, Jens et al. · Sci Adv · 2022

basic_science · Level V

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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.