title: Structure and membrane remodeling activity of ESCRT-III helical polymers.
abstract: The endosomal sorting complexes required for transport (ESCRT) proteins mediate fundamental membrane remodeling events that require stabilizing negative membrane curvature. These include endosomal intralumenal vesicle formation, HIV budding, nuclear envelope closure, and cytokinetic abscission. ESCRT-III subunits perform key roles in these processes by changing conformation and polymerizing into membrane-remodeling filaments. Here, we report the 4 angstrom resolution cryogenic electron microscopy reconstruction of a one-start, double-stranded helical copolymer composed of two different human ESCRT-III subunits, charged multivesicular body protein 1B (CHMP1B) and increased sodium tolerance 1 (IST1). The inner strand comprises "open" CHMP1B subunits that interlock in an elaborate domain-swapped architecture and is encircled by an outer strand of "closed" IST1 subunits. Unlike other ESCRT-III proteins, CHMP1B and IST1 polymers form external coats on positively curved membranes in vitro and in vivo. Our analysis suggests how common ESCRT-III filament architectures could stabilize different degrees and directions of membrane curvature.
authors.affiliation: Department of Biochemistry, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: John
authors.initials: J
authors.lastname: McCullough
authors.affiliation: Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Amy K
authors.initials: AK
authors.lastname: Clippinger
authors.affiliation: Department of Biochemistry, University of Utah, Salt Lake City, UT 84112, USA. Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Talledge
authors.affiliation: Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Skowyra
authors.affiliation: Department of Biochemistry, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Marissa G
authors.initials: MG
authors.lastname: Saunders
authors.affiliation: Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Teresa V
authors.initials: TV
authors.lastname: Naismith
authors.affiliation: Department of Biochemistry, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Leremy A
authors.initials: LA
authors.lastname: Colf
authors.affiliation: Physical Bioscience Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Pavel
authors.initials: P
authors.lastname: Afonine
authors.affiliation: FEI Company, Hillsboro, OR 97124, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Arthur
authors.affiliation: Department of Biochemistry, University of Utah, Salt Lake City, UT 84112, USA. wes@biochem.utah.edu phanson22@wustl.edu adam.frost@ucsf.edu.
authors.forename: Wesley I
authors.initials: WI
authors.lastname: Sundquist
authors.affiliation: Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA. wes@biochem.utah.edu phanson22@wustl.edu adam.frost@ucsf.edu.
authors.forename: Phyllis I
authors.initials: PI
authors.lastname: Hanson
authors.affiliation: Department of Biochemistry, University of Utah, Salt Lake City, UT 84112, USA. Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA. wes@biochem.utah.edu phanson22@wustl.edu adam.frost@ucsf.edu.
authors.forename: Adam
authors.initials: A
authors.lastname: Frost
mesh_terms: D001704:Biopolymers / Q000737:chemistry; D002462:Cell Membrane / Q000737:chemistry / Q000648:ultrastructure; D020285:Cryoelectron Microscopy; D056827:Endosomal Sorting Complexes Required for Transport / Q000737:chemistry*; D006801:Humans; D015513:Oncogene Proteins / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D001704:Biopolymers; C541483:CHMP1B protein, human; C481529:CHMP4A protein, human; D056827:Endosomal Sorting Complexes Required for Transport; C533705:IST1 protein, human; D015513:Oncogene Proteins