title: Structural insights into the organization of the cavin membrane coat complex.
abstract: Caveolae are cell-surface membrane invaginations that play critical roles in cellular processes including signaling and membrane homeostasis. The cavin proteins, in cooperation with caveolins, are essential for caveola formation. Here we show that a minimal N-terminal domain of the cavins, termed HR1, is required and sufficient for their homo- and hetero-oligomerization. Crystal structures of the mouse cavin1 and zebrafish cavin4a HR1 domains reveal highly conserved trimeric coiled-coil architectures, with intersubunit interactions that determine the specificity of cavin-cavin interactions. The HR1 domain contains a basic surface patch that interacts with polyphosphoinositides and coordinates with additional membrane-binding sites within the cavin C terminus to facilitate membrane association and remodeling. Electron microscopy of purified cavins reveals the existence of large assemblies, composed of a repeating rod-like structural element, and we propose that these structures polymerize through membrane-coupled interactions to form the unique striations observed on the surface of caveolae in vivo.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia.
authors.forename: Oleksiy
authors.initials: O
authors.lastname: Kovtun
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia.
authors.forename: Vikas A
authors.initials: VA
authors.lastname: Tillu
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia.
authors.forename: WooRam
authors.initials: W
authors.lastname: Jung
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia.
authors.forename: Natalya
authors.initials: N
authors.lastname: Leneva
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Ariotti
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia.
authors.forename: Natasha
authors.initials: N
authors.lastname: Chaudhary
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia.
authors.forename: Ramya A
authors.initials: RA
authors.lastname: Mandyam
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia.
authors.forename: Charles
authors.initials: C
authors.lastname: Ferguson
authors.affiliation: Centre for Microscopy and Microanalysis, The University of Queensland, St. Lucia, QLD 4072, Australia.
authors.forename: Garry P
authors.initials: GP
authors.lastname: Morgan
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia.
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Johnston
authors.affiliation: School of Physics, The University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Harrop
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia.
authors.forename: Kirill
authors.initials: K
authors.lastname: Alexandrov
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia; Centre for Microscopy and Microanalysis, The University of Queensland, St. Lucia, QLD 4072, Australia. Electronic address: r.parton@imb.uq.edu.au.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Parton
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia. Electronic address: b.collins@imb.uq.edu.au.
authors.forename: Brett M
authors.initials: BM
authors.lastname: Collins
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D021941:Caveolae / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D022461:Caveolins / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D020836:Protein Structure, Quaternary; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D015027:Zebrafish / Q000378:metabolism
chemical_list: D022461:Caveolins; D008565:Membrane Proteins; D016601:RNA-Binding Proteins