3UL0

Mouse importin alpha: mouse CBP80Y8D cNLS complex

Summary for 3UL0

• Entry DOI: 10.2210/pdb3ul0/pdb
• Related: 1IAL 3FEX 3FEY 3UKW 3UKX 3UKY 3UKZ 3UL1
• Descriptor: Importin subunit alpha-2, Nuclear cap-binding protein subunit 1 (3 entities in total)
• Functional Keywords: arm repeat, armadillo repeat, nuclear transport, nuclear localisation signal binding, importin beta binding, protein transport-protein binding complex, protein transport/protein binding
• Biological source: Mus musculus (mouse); More
• Cellular location: Cytoplasm (By similarity): P52293; Nucleus (By similarity): Q3UYV9
• Total number of polymer chains: 2
• Total formula weight: 58172.60

Authors

Marfori, M.,Forwood, J.K.,Lonhienne, T.G.,Kobe, B. (deposition date: 2011-11-10, release date: 2012-10-03, Last modification date: 2023-11-01)

Primary citation

Marfori, M.,Lonhienne, T.G.,Forwood, J.K.,Kobe, B.
Structural Basis of High-Affinity Nuclear Localization Signal Interactions with Importin-alpha
Traffic, 13:532-548, 2012

PubMed Abstract: Classical nuclear localization signals (cNLSs), comprising one (monopartite cNLSs) or two clusters of basic residues connected by a 10-12 residue linker (bipartite cNLSs), are recognized by the nuclear import factor importin-α. The cNLSs bind along a concave groove on importin-α; however, specificity determinants of cNLSs remain poorly understood. We present a structural and interaction analysis study of importin-α binding to both designed and naturally occurring high-affinity cNLS-like sequences; the peptide inhibitors Bimax1 and Bimax2, and cNLS peptides of cap-binding protein 80. Our data suggest that cNLSs and cNLS-like sequences can achieve high affinity through maximizing interactions at the importin-α minor site, and by taking advantage of multiple linker region interactions. Our study defines an extended set of binding cavities on the importin-α surface, and also expands on recent observations that longer linker sequences are allowed, and that long-range electrostatic complementarity can contribute to cNLS-binding affinity. Altogether, our study explains the molecular and structural basis of the results of a number of recent studies, including systematic mutagenesis and peptide library approaches, and provides an improved level of understanding on the specificity determinants of a cNLS. Our results have implications for identifying cNLSs in novel proteins.

PubMed: 22248489
DOI: 10.1111/j.1600-0854.2012.01329.x

Experimental method

X-RAY DIFFRACTION (2 Å)