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Title: Crystal structure of importin-α3 bound to the nuclear localization signal of Ran-binding protein 3

Abstract

Ran-binding protein 3 (RanBP3) is a primarily nuclear Ran-binding protein that functions as an accessory factor in the Ran GTPase system. RanBP3 associates with Ran-specific nucleotide exchange factor RCC1 and enhances its catalytic activity towards Ran. RanBP3 also promotes CRM1-mediated nuclear export as well as CRM1-independent nuclear export of β-catenin, Smad2, and Smad3. Nuclear import of RanBP3 is dependent on the nuclear import adaptor protein importin-α and, RanBP3 is imported more efficiently by importin-α3 than by other members of the importin-α family. Protein kinase signaling pathways control nucleocytoplasmic transport through phosphorylation of RanBP3 at Ser58, immediately C-terminal to the nuclear localization signal (NLS) in the N-terminal region of RanBP3. Here we report the crystal structure of human importin-α3 bound to an N-terminal fragment of human RanBP3 containing the NLS sequence that is necessary and sufficient for nuclear import. The structure reveals that RanBP3 binds to importin-α3 residues that are strictly conserved in all seven isoforms of human importin-α at the major NLS-binding site, indicating that the region of importin-α outside the NLS-binding site, possibly the autoinhibotory importin-β1-binding domain, may be the key determinant for the preferential binding of RanBP3 to importin-α3. Computational docking simulation indicates that phosphorylation of RanBP3 atmore » Ser58 could potentially stabilize the association of RanBP3 with importin-α through interactions between the phosphate moiety of phospho-Ser58 of RanBP3 and a cluster of basic residues (Arg96 and Lys97 in importin-α3) on armadillo repeat 1 of importin-α. - Highlights: • Ran-binding protein 3 (RanBP3) is an accessory factor in the Ran GTPase system. • The N-terminal region of RanBP3 contains a nuclear localization signal (NLS). • Crystal structure of importin-α3 bound to the NLS of RanBP3 is solved. • Phosphorylation of RanBP3 at Ser58 may modulate binding affinity to importin-α.« less

Authors:
 [1];  [1]
  1. Division of Biological Science, Graduate School of Science, Nagoya University (Japan)
Publication Date:
OSTI Identifier:
22719084
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 491; Journal Issue: 3; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AFFINITY; CRYSTAL STRUCTURE; NUCLEOTIDES; PHOSPHATES; PHOSPHORYLATION; PHOSPHOTRANSFERASES; SIMULATION

Citation Formats

Koyama, Masako, Matsuura, Yoshiyuki, and Structural Biology Research Center, Graduate School of Science, Nagoya University. Crystal structure of importin-α3 bound to the nuclear localization signal of Ran-binding protein 3. United States: N. p., 2017. Web. doi:10.1016/J.BBRC.2017.07.155.
Koyama, Masako, Matsuura, Yoshiyuki, & Structural Biology Research Center, Graduate School of Science, Nagoya University. Crystal structure of importin-α3 bound to the nuclear localization signal of Ran-binding protein 3. United States. doi:10.1016/J.BBRC.2017.07.155.
Koyama, Masako, Matsuura, Yoshiyuki, and Structural Biology Research Center, Graduate School of Science, Nagoya University. Sat . "Crystal structure of importin-α3 bound to the nuclear localization signal of Ran-binding protein 3". United States. doi:10.1016/J.BBRC.2017.07.155.
@article{osti_22719084,
title = {Crystal structure of importin-α3 bound to the nuclear localization signal of Ran-binding protein 3},
author = {Koyama, Masako and Matsuura, Yoshiyuki and Structural Biology Research Center, Graduate School of Science, Nagoya University},
abstractNote = {Ran-binding protein 3 (RanBP3) is a primarily nuclear Ran-binding protein that functions as an accessory factor in the Ran GTPase system. RanBP3 associates with Ran-specific nucleotide exchange factor RCC1 and enhances its catalytic activity towards Ran. RanBP3 also promotes CRM1-mediated nuclear export as well as CRM1-independent nuclear export of β-catenin, Smad2, and Smad3. Nuclear import of RanBP3 is dependent on the nuclear import adaptor protein importin-α and, RanBP3 is imported more efficiently by importin-α3 than by other members of the importin-α family. Protein kinase signaling pathways control nucleocytoplasmic transport through phosphorylation of RanBP3 at Ser58, immediately C-terminal to the nuclear localization signal (NLS) in the N-terminal region of RanBP3. Here we report the crystal structure of human importin-α3 bound to an N-terminal fragment of human RanBP3 containing the NLS sequence that is necessary and sufficient for nuclear import. The structure reveals that RanBP3 binds to importin-α3 residues that are strictly conserved in all seven isoforms of human importin-α at the major NLS-binding site, indicating that the region of importin-α outside the NLS-binding site, possibly the autoinhibotory importin-β1-binding domain, may be the key determinant for the preferential binding of RanBP3 to importin-α3. Computational docking simulation indicates that phosphorylation of RanBP3 at Ser58 could potentially stabilize the association of RanBP3 with importin-α through interactions between the phosphate moiety of phospho-Ser58 of RanBP3 and a cluster of basic residues (Arg96 and Lys97 in importin-α3) on armadillo repeat 1 of importin-α. - Highlights: • Ran-binding protein 3 (RanBP3) is an accessory factor in the Ran GTPase system. • The N-terminal region of RanBP3 contains a nuclear localization signal (NLS). • Crystal structure of importin-α3 bound to the NLS of RanBP3 is solved. • Phosphorylation of RanBP3 at Ser58 may modulate binding affinity to importin-α.},
doi = {10.1016/J.BBRC.2017.07.155},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 491,
place = {United States},
year = {2017},
month = {9}
}