Arx1 functions as an unorthodox nuclear export receptor for the 60S preribosomal subunit.
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.
Bradatsch
Bettina
B
Biochemie-Zentrum der Universität Heidelberg, Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany.
Katahira
Jun
J
Kowalinski
Eva
E
Bange
Gert
G
Yao
Wei
W
Sekimoto
Toshihiro
T
Baumgärtel
Viola
V
Boese
Guido
G
Bassler
Jochen
J
Wild
Klemens
K
Peters
Reiner
R
Yoneda
Yoshihiro
Y
Sinning
Irmi
I
Hurt
Ed
E
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