20.500.12556/DiRROS-22223 Cryo-EM structures of a protein pore reveal a cluster of cholesterol molecules and diverse roles of membrane lipids The structure and function of membrane proteins depend on their interactions with lipids that constitute membranes. Actinoporins are α-pore-forming proteins that bind preferentially to sphingomyelin-containing membranes, where they oligomerize and form transmembrane pores. Through a comprehensive cryo-electron microscopic analysis of a pore formed by an actinoporin Fav from the coral Orbicella faveolata, we show that the octameric pore interacts with 112 lipids in the upper leaflet of the membrane, reveal the roles of lipids, and demonstrate that the actinoporin surface is suited for binding multiple receptor sphingomyelin molecules. When cholesterol is present in the membrane, it forms a cluster of four molecules associated with each protomer. Atomistic simulations support the structural data and reveal additional effects of the pore on the lipid membrane. These data reveal a complex network of protein-lipid and lipid-lipid interactions and an underrated role of lipids in the structure and function of transmembrane protein complexes. biokemija lipidi beljakovine membrane mikroskopske analize true false true Angleški jezik Slovenski jezik © The Author(s) 2025 Neznano 2025-05-12 09:01:32 2025-05-12 09:43:35 2025-10-24 03:50:50 0000-00-00 00:00:00 2025 0 0 Nasl. z nasl. zaslona; Opis vira z dne 9. 5. 2025; str. 1-11 article no. 2972 Vol. 16 2025 0000-00-00 Zaloznikova Objavljeno apc 0000-00-00 0000-00-00 2025-01-01 577 2041-1723 10.1038/s41467-025-58334-z 235400707 https://www.nature.com/articles/s41467-025-58334-z 1 f17231aa-2efe-11f0-963a-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=32166 RAZ_Solinc_Gasper_2025.pdf RAZ_Solinc_Gasper_2025.pdf 1 65BE545EF338BB88EFEF724C22D8570C 43ef87da95a03cb14c3369e3348ba389ec57cb553cc1d1afdea5f2792da400c4 3cbd889b-2f04-11f0-963a-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=32167 Kemijski inštitut 0 0 0