期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：50
页码：E8069-E8078
DOI：10.1073/pnas.1616838113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceThe surface of mammalian cells contains abundant plasma membrane invaginations termed "caveolae." Caveolae are important for various cellular functions, e.g. signaling, membrane regulation, and vesicular trafficking. Assembly and stability of caveolae depends on a protein coat formed by complexes of cavin and caveolin proteins whose structure has remained elusive. To understand the architecture of caveolae, we structurally analyzed cavin and caveolin complexes and visualized caveolae in cells by electron cryomicroscopy. A regular polyhedron emerged as the most likely architectural principle of caveolae. Polyhedra provide the underlying principle in many biological structures in which spherical curvature is imposed by proteins. We suggest a model for the caveolar coat architecture based on regularly arranged, net-like cavin assemblies and disc-shaped caveolin oligomers. Caveolae are invaginated plasma membrane domains involved in mechanosensing, signaling, endocytosis, and membrane homeostasis. Oligomers of membrane-embedded caveolins and peripherally attached cavins form the caveolar coat whose structure has remained elusive. Here, purified Cavin1 60S complexes were analyzed structurally in solution and after liposome reconstitution by electron cryotomography. Cavin1 adopted a flexible, net-like protein mesh able to form polyhedral lattices on phosphatidylserine-containing vesicles. Mutating the two coiled-coil domains in Cavin1 revealed that they mediate distinct assembly steps during 60S complex formation. The organization of the cavin coat corresponded to a polyhedral nano-net held together by coiled-coil segments. Positive residues around the C-terminal coiled-coil domain were required for membrane binding. Purified caveolin 8S oligomers assumed disc-shaped arrangements of sizes that are consistent with the discs occupying the faces in the caveolar polyhedra. Polygonal caveolar membrane profiles were revealed in tomograms of native caveolae inside cells. We propose a model with a regular dodecahedron as structural basis for the caveolae architecture.
