title: Structural basis for budding by the ESCRT-III factor CHMP3.
abstract: The vacuolar protein sorting machinery regulates multivesicular body biogenesis and is selectively recruited by enveloped viruses to support budding. Here we report the crystal structure of the human ESCRT-III protein CHMP3 at 2.8 A resolution. The core structure of CHMP3 folds into a flat helical arrangement that assembles into a lattice, mainly via two different dimerization modes, and unilaterally exposes a highly basic surface. The C terminus, the target for Vps4-induced ESCRT disassembly, extends from the opposite side of the membrane targeting region. Mutations within the basic and dimerization regions hinder bilayer interaction in vivo and reverse the dominant-negative effect of a truncated CHMP3 fusion protein on HIV-1 budding. Thus, the final steps in the budding process may include CHMP protein polymerization and lattice formation on membranes by employing different bilayer-recognizing surfaces, a function shared by all CHMP family members.
authors.affiliation: European Molecular Biology Laboratory, 6 rue Jules Horowitz, 38042 Grenoble, France.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Muzioł
authors.forename: Estela
authors.initials: E
authors.lastname: Pineda-Molina
authors.forename: Raimond B
authors.initials: RB
authors.lastname: Ravelli
authors.forename: Alessia
authors.initials: A
authors.lastname: Zamborlini
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Usami
authors.forename: Heinrich
authors.initials: H
authors.lastname: Göttlinger
authors.forename: Winfried
authors.initials: W
authors.lastname: Weissenhorn
mesh_terms: D000595:Amino Acid Sequence; D024342:Amino Acids, Acidic / Q000737:chemistry; D024361:Amino Acids, Basic / Q000737:chemistry; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D019281:Dimerization; D056827:Endosomal Sorting Complexes Required for Transport; D015658:HIV Infections / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity; D033921:Vesicular Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D024342:Amino Acids, Acidic; D024361:Amino Acids, Basic; C498543:CHMP3 protein, human; D056827:Endosomal Sorting Complexes Required for Transport; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D033921:Vesicular Transport Proteins