5XZX

Crystal structure of importin-alpha3 bound to the nuclear localization signal of Ran-binding protein 3

Summary for 5XZX

• Entry DOI: 10.2210/pdb5xzx/pdb
• Descriptor: Importin subunit alpha-3, Ran-binding protein 3 (2 entities in total)
• Functional Keywords: nuclear import, transport protein
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm : O00629 Q9H6Z4
• Total number of polymer chains: 2
• Total formula weight: 48991.46

Authors

Koyama, M.,Matsuura, Y. (deposition date: 2017-07-14, release date: 2017-08-09, Last modification date: 2023-11-22)

Primary citation

Koyama, M.,Matsuura, Y.
Crystal structure of importin-alpha 3 bound to the nuclear localization signal of Ran-binding protein 3
Biochem. Biophys. Res. Commun., 491:609-613, 2017

PubMed 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 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.

PubMed: 28760339
DOI: 10.1016/j.bbrc.2017.07.155

Experimental method

X-RAY DIFFRACTION (3 Å)