Sci. STKE, 3 May 2005
Subcellular Localization Signal Sends Carrier to the Nucleus
The intracellular lipid-binding proteins (iLBPs) are thought to act as carriers that move small lipophilic compounds in the cell. Cellular retinoic acid binding protein-II (CRABP-II) is one such protein and helps augment the biological effects of retinoic acid to activate the type II nuclear receptor known as the retinoic acid receptor (RAR). CRABP-II is thought to interact with RARs also and, in essence, to hand off the retinoic acid ligand to its receptor. RARs are localized in the nucleus, and CRABP-II is found in the cytoplasm but moves to the nucleus when it binds retinoic acid. However CRABP-II contains no classical nuclear localization signal, so it has been unclear how this translocation occurs. Sessier and Noy therefore examined the crystal structures of ligand-bound and -unbound CRABP-II for differences that might account for the translocation. Comparison of combined electrostatic surface potentials across the molecular surfaces of the two proteins revealed a region that was neutrally charged in the unbound protein but became basic or positively charged when retinoic acid was bound. Furthermore, it appeared that reorganization of three key basic amino acid residues brought them into an alignment that approximates that seen in the primary sequence of a classical nuclear localization sequence. Mutations in these residues prevented nuclear localization of CRABP-II, its interaction with importin alpha (a component of the nuclear translocation machinery), and its ability to enhance transcription mediated by RAR. Thus CRABP-II appears to contain a ligand-regulated switch that determines its subcellular localization.
R. J. Sessler, N. Noy, A ligand-activated nuclear localization signal in cellular retinoic acid binding protein-II. Mol. Cell 18, 343-353 (2005). [Online Journal]
Citation: Signal Sends Carrier to the Nucleus. Sci. STKE 2005, tw169 (2005).
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