Molecular basis for the recognition of a nonclassical nuclear localization signal by importin beta.

Nuclear import of proteins containing a classical nuclear localization signal (NLS) involves NLS recognition by importin alpha, which associates with importin beta via the IBB domain. Other proteins, including parathyroid hormone-related protein (PTHrP), are imported into the nucleus by direct interaction with importin beta. We solved the crystal structure of ...
a fragment of importin beta-1 (1-485) bound to the nonclassical NLS of PTHrP. The structure reveals a second extended cargo binding site on importin beta distinct from the IBB domain binding site. Using a permeabilized cell import assay we demonstrate that importin beta (1-485) can import PTHrP-coupled cargo in a Ran-dependent manner. We propose that this region contains a prototypical nuclear import receptor domain, which could have evolved into the modern importin beta superfamily.
Mesh Terms:
Active Transport, Cell Nucleus, Amino Acid Sequence, Binding Sites, Cell Nucleus, Cloning, Molecular, Crystallography, X-Ray, Escherichia coli, Hela Cells, Humans, Models, Molecular, Molecular Sequence Data, Parathyroid Hormone-Related Protein, Peptide Fragments, Peptide Hormones, Phosphorylation, Protein Structure, Secondary, Recombinant Proteins, Repetitive Sequences, Amino Acid, Signal Transduction, Static Electricity, Surface Properties, beta Karyopherins
Mol. Cell
Date: Dec. 01, 2002
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