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TitleEvolutionarily diverse caveolins share a common structural framework built around amphipathic disks.
Journal, issue, pagesJ Cell Biol, Vol. 224, Issue 9, Year 2025
Publish dateSep 1, 2025
AuthorsBing Han / Sarah M Connolly / Darrin T Schultz / Louis F L Wilson / Alican Gulsevin / Jens Meiler / Erkan Karakas / Melanie D Ohi / Anne K Kenworthy /
PubMed AbstractCaveolins are a unique family of membrane remodeling proteins present broadly across animals (Metazoa), and in vertebrates form flask-shaped invaginations known as caveolae. While human caveolin-1 ...Caveolins are a unique family of membrane remodeling proteins present broadly across animals (Metazoa), and in vertebrates form flask-shaped invaginations known as caveolae. While human caveolin-1 assembles into an amphipathic disk composed of 11 spirally packed protomers, the structural basis underlying caveolin function across animals remains elusive. Here, we predicted structures for 73 caveolins spanning animal diversity, as well as a newly identified choanoflagellate caveolin from Salpingoeca rosetta. This analysis revealed seven conserved structural elements and a propensity to assemble into amphipathic disks. Cryo-EM structures of caveolins from S. rosetta choanoflagellate and the purple sea urchin Strongylocentrotus purpuratus exhibit striking structural similarities to human caveolin-1, validating the structural predictions. Lastly, tracing the chromosomal evolutionary history of caveolins revealed its parahoxozoan ancestral chromosome and evolutionary branches on which caveolins translocated and expanded. These results show that caveolins possess an ancient structural framework predating Metazoa and provide a new structural paradigm to explore the molecular basis of caveolin function across diverse evolutionary lineages.
External linksJ Cell Biol / PubMed:40772930 / PubMed Central
MethodsEM (single particle)
Resolution2.9 - 3.1 Å
Structure data

EMDB-47022, PDB-9dn0:
CryoEM structure of the Strongylocentrotus purpuratus caveolin complex
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-47023, PDB-9dn1:
CryoEM structure of the Salpingoeca rosetta caveolin complex
Method: EM (single particle) / Resolution: 2.9 Å

Source
  • strongylocentrotus purpuratus (purple sea urchin)
  • salpingoeca rosetta (eukaryote)
KeywordsMEMBRANE PROTEIN / Membrane-shaping protein / monotopic membrane protein / monotonic membrane protein

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