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

Abstract:

: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.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Cingolani G,Bednenko J,Gillespie MT,Gerace L

doi

10.1016/s1097-2765(02)00727-x

subject

Has Abstract

pub_date

2002-12-01 00:00:00

pages

1345-53

issue

6

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(02)00727-X

journal_volume

10

pub_type

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