title: Arx1 functions as an unorthodox nuclear export receptor for the 60S preribosomal subunit.
abstract: Shuttling transport receptors carry cargo through nuclear pore complexes (NPCs) via transient interactions with Phe-Gly (FG)-rich nucleoporins. Here, we identify Arx1, a factor associated with a late 60S preribosomal particle in the nucleus, as an unconventional export receptor. Arx1 binds directly to FG nucleoporins and exhibits facilitated translocation through NPCs. Moreover, Arx1 functionally overlaps with the other 60S export receptors, Xpo1 and Mex67-Mtr2, and is genetically linked to nucleoporins. Unexpectedly, Arx1 is structurally unrelated to known shuttling transport receptors but homologous to methionine aminopeptidases (MetAPs), however, without enzymatic activity. Typically, the MetAP fold creates a central cavity that binds the methionine. In contrast, the predicted central cavity of Arx1 is involved in the interaction with FG repeat nucleoporins and 60S subunit export. Thus, an ancient enzyme fold has been adopted by Arx1 to function as a nuclear export receptor.
authors.affiliation: Biochemie-Zentrum der Universität Heidelberg, Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Bradatsch
authors.forename: Jun
authors.initials: J
authors.lastname: Katahira
authors.forename: Eva
authors.initials: E
authors.lastname: Kowalinski
authors.forename: Gert
authors.initials: G
authors.lastname: Bange
authors.forename: Wei
authors.initials: W
authors.lastname: Yao
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sekimoto
authors.forename: Viola
authors.initials: V
authors.lastname: Baumgärtel
authors.forename: Guido
authors.initials: G
authors.lastname: Boese
authors.forename: Jochen
authors.initials: J
authors.lastname: Bassler
authors.forename: Klemens
authors.initials: K
authors.lastname: Wild
authors.forename: Reiner
authors.initials: R
authors.lastname: Peters
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yoneda
authors.forename: Irmi
authors.initials: I
authors.lastname: Sinning
authors.forename: Ed
authors.initials: E
authors.lastname: Hurt
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D022022:Nuclear Pore / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000502:physiology*; D012269:Ribosomal Proteins / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D016415:Sequence Alignment