1m5n
From Proteopedia
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Crystal structure of HEAT repeats (1-11) of importin b bound to the non-classical NLS(67-94) of PTHrP
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Overview
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.
Disease
Known disease associated with this structure: Humoral hypercalcemia of malignancy (1) OMIM:[168470]
About this Structure
1M5N is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Molecular basis for the recognition of a nonclassical nuclear localization signal by importin beta., Cingolani G, Bednenko J, Gillespie MT, Gerace L, Mol Cell. 2002 Dec;10(6):1345-53. PMID:12504010
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