title: ESCRT-III activation by parallel action of ESCRT-I/II and ESCRT-0/Bro1 during MVB biogenesis.
abstract: The endosomal sorting complexes required for transport (ESCRT) pathway facilitates multiple fundamental membrane remodeling events. Previously, we determined X-ray crystal structures of ESCRT-III subunit Snf7, the yeast CHMP4 ortholog, in its active and polymeric state (Tang et al., 2015). However, how ESCRT-III activation is coordinated by the upstream ESCRT components at endosomes remains unclear. Here, we provide a molecular explanation for the functional divergence of structurally similar ESCRT-III subunits. We characterize novel mutations in ESCRT-III Snf7 that trigger activation, and identify a novel role of Bro1, the yeast ALIX ortholog, in Snf7 assembly. We show that upstream ESCRTs regulate Snf7 activation at both its N-terminal core domain and the C-terminus α6 helix through two parallel ubiquitin-dependent pathways: the ESCRT-I-ESCRT-II-Vps20 pathway and the ESCRT-0-Bro1 pathway. We therefore provide an enhanced understanding for the activation of the spatially unique ESCRT-III-mediated membrane remodeling.
authors.affiliation: Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, United States.|Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States.
authors.forename: Shaogeng
authors.identifier: 0000-0002-3904-492X
authors.initials: S
authors.lastname: Tang
authors.affiliation: Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, United States.|Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Buchkovich
authors.affiliation: Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, United States.|Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States.
authors.forename: W Mike
authors.initials: WM
authors.lastname: Henne
authors.affiliation: Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, United States.|Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States.
authors.forename: Sudeep
authors.initials: S
authors.lastname: Banjade
authors.affiliation: Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, United States.|Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States.
authors.forename: Yun Jung
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, United States.|Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States.
authors.forename: Scott D
authors.identifier: 0000-0002-5408-6781
authors.initials: SD
authors.lastname: Emr
mesh_terms: D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D057146:Multivesicular Bodies / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D009154:Mutation; D000072417:Protein Domains; D017433:Protein Structure, Secondary; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D057149:Ubiquitinated Proteins / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination
chemical_list: C480237:Bro1 protein, S cerevisiae; D056827:Endosomal Sorting Complexes Required for Transport; C083890:SNF7 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D057149:Ubiquitinated Proteins
keywords: Bro1; ESCRT-I; ESCRT-II; ESCRT-III; S. cerevisiae; Snf7; activation; biochemistry; cell biology