A ligand-activated nuclear localization signal in cellular retinoic acid binding protein-II.
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 NLS, 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 NLS 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 NLS in holo- but not apo-CRABP-II. The signal, whose three-dimensional configuration aligns strikingly well with a "classical" NLS, mediates ligand-induced association of CRABP-II with importin alpha and is critical for nuclear localization of the protein. The ligand-controlled NLS "switch" of CRABP-II may represent a general mechanism for posttranslational regulation of the subcellular distribution of a protein.
Sessler
Richard J
RJ
Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA.
Noy
Noa
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D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals; D017434:Protein Structure, Tertiary; D018168:Receptors, Retinoic Acid / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014212:Tretinoin / Q000378:metabolism; D028901:alpha Karyopherins / Q000378:metabolism
D008024:Ligands; D019913:Nuclear Localization Signals; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins; D028901:alpha Karyopherins; C082928:retinoic acid binding protein II, cellular; D014212:Tretinoin