3Q5U: A minimal NLS from human scramblase 4 complexed with importin alpha

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, whereas 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 alpha. 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 nonclassical cargos.
PDB ID: 3Q5UDownload
MMDB ID: 91867
PDB Deposition Date: 2010/12/29
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2.5  Å
Source Organism:
Mus musculus
Similar Structures:
Biological Unit for 3Q5U: dimeric; determined by author
Molecular Components in 3Q5U
Label Count Molecule
Proteins (2 molecules)
Importin Subunit Alpha-2(Gene symbol: Kpna2)
Molecule annotation
Phospholipid Scramblase 4(Gene symbol: PLSCR4)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB