[PDF][PDF] Molecular basis for the recognition of a nonclassical nuclear localization signal by importin β

G Cingolani, J Bednenko, MT Gillespie, L Gerace - Molecular cell, 2002 - cell.com
G Cingolani, J Bednenko, MT Gillespie, L Gerace
Molecular cell, 2002cell.com
Nuclear import of proteins containing a classical nuclear localization signal (NLS) involves
NLS recognition by importin α, which associates with importin β via the IBB domain. Other
proteins, including parathyroid hormone-related protein (PTHrP), are imported into the
nucleus by direct interaction with importin β. We solved the crystal structure of a fragment of
importin β-1 (1–485) bound to the nonclassical NLS of PTHrP. The structure reveals a
second extended cargo binding site on importin β distinct from the IBB domain binding site …
Abstract
Nuclear import of proteins containing a classical nuclear localization signal (NLS) involves NLS recognition by importin α, which associates with importin β via the IBB domain. Other proteins, including parathyroid hormone-related protein (PTHrP), are imported into the nucleus by direct interaction with importin β. We solved the crystal structure of a fragment of importin β-1 (1–485) bound to the nonclassical NLS of PTHrP. The structure reveals a second extended cargo binding site on importin β distinct from the IBB domain binding site. Using a permeabilized cell import assay we demonstrate that importin β (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 β superfamily.
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