title: Activation of the retroviral budding factor ALIX.
abstract: The cellular ALIX protein functions within the ESCRT pathway to facilitate intralumenal endosomal vesicle formation, the abscission stage of cytokinesis, and enveloped virus budding. Here, we report that the C-terminal proline-rich region (PRR) of ALIX folds back against the upstream domains and auto-inhibits V domain binding to viral late domains. Mutations designed to destabilize the closed conformation of the V domain opened the V domain, increased ALIX membrane association, and enhanced virus budding. These observations support a model in which ALIX activation requires dissociation of the autoinhibitory PRR and opening of the V domain arms.
authors.affiliation: Department of Biochemistry, University of Utah School of Medicine, 15 N. Medical Drive East, Salt Lake City, UT 84112-5650, USA.
authors.forename: Qianting
authors.initials: Q
authors.lastname: Zhai
authors.forename: Michael B
authors.initials: MB
authors.lastname: Landesman
authors.forename: Hyo-Young
authors.initials: HY
authors.lastname: Chung
authors.forename: Adam
authors.initials: A
authors.lastname: Dierkers
authors.forename: Cy M
authors.initials: CM
authors.lastname: Jeffries
authors.forename: Jill
authors.initials: J
authors.lastname: Trewhella
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Hill
authors.forename: Wesley I
authors.initials: WI
authors.lastname: Sundquist
mesh_terms: D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D056827:Endosomal Sorting Complexes Required for Transport / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008958:Models, Molecular; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D053838:Scattering, Small Angle; D057074:Virus Release
chemical_list: D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D050505:Mutant Proteins; C117020:PDCD6IP protein, human