A ligand-activated nuclear localization signal in cellular retinoic acid binding protein-II

A ligand-activated nuclear localization signal in cellular retinoic acid binding protein-II
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DOI:
10.1016/j.molcel.2005.03.026
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发表时间:
2005-04-29
期刊:
影响因子:
16
通讯作者:
Noy, N
Noy, N
中科院分区:
生物学1区
文献类型:
--
作者:
Sessler, RJ;Noy, N

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Primary sequences of proteins often contain motifs that serve as "signatures" for subcellular targeting, such as a nuclear localization signal (NLS). However, many nuclear proteins do not harbor a recognizable NILS, and the pathways that mediate their nuclear translocation are unknown. This work focuses on CRABP-II, a cytosolic protein that moves to the nucleus upon binding of retinoic acid. While CRABP-II does not contain an NILS in its primary sequence, such a motif could be recognized in the protein's tertiary structure. We map the retinoic acid-induced structural rearrangements that result in the presence of this NILS in holo- but not apo-CRABP-II. The signal, whose three-dimensional configuration aligns strikingly well with a "classical" NILS, mediates ligand-induced association of CRABP-II with importin a and is critical for nuclear localization of the protein. The ligand-controlled NILS "switch" of CRABP-II may represent a general mechanism for posttranslational regulation of the subcellular distribution of a protein.