Structural highlights
Function
[IMA2_MOUSE] Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. [PLS4_HUMAN] May mediate accelerated ATP-independent bidirectional transbilayer migration of phospholipids upon binding calcium ions that results in a loss of phospholipid asymmetry in the plasma membrane. May play a central role in the initiation of fibrin clot formation, in the activation of mast cells and in the recognition of apoptotic and injured cells by the reticuloendothelial system.
Publication Abstract from PubMed
Importin alpha1 can bind classical nuclear localization signals (NLSs) in two NLS-binding sites, known as 'major' and 'minor'. The major site is located between ARM repeats 2-4, while the minor site spans ARM 7-8. In this study, we have characterized the cellular localization of human phospholipid scramblase 4 (hPLSCR4), a member of the phospholipid scramblase protein family. We identified a minimal NLS in hPLSCR4 ((273)GSIIRKWN(280)) that contains only two basic amino acids. This NLS is both necessary for nuclear localization of hPLSCR4 in transfected HeLa cells and sufficient for nuclear import of a non-diffusible cargo in permeabilized cells. Mutation of only one of the two basic residues, Arg(277), correlates with loss of nuclear localization, suggesting this amino acid plays a key role in nuclear transport. Crystallographic analysis of mammalian importin alpha1 in complex with the hPLSCR4-NLS reveals this minimal NLS binds specifically and exclusively to the minor binding site of importin alpha1. These data provide the first structural and functional evidence of a novel NLS-binding mode in importin alpha1 that uses only the minor groove as the exclusive site for nuclear import of non classical cargos.
A minimal NLS in human phospholipid scramblase 4 that binds only the minor NLS-binding site of importin {alpha}1.,Lott K, Bhardwaj A, Sims PJ, Cingolani G J Biol Chem. 2011 Jun 20. PMID:21690087[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lott K, Bhardwaj A, Sims PJ, Cingolani G. A minimal NLS in human phospholipid scramblase 4 that binds only the minor NLS-binding site of importin {alpha}1. J Biol Chem. 2011 Jun 20. PMID:21690087 doi:10.1074/jbc.M111.228007
