3OQS: Crystal Structure Of Importin-Alpha Bound To A Clic4 Nls Peptide

Citation:
Abstract
It has been reported that a human chloride intracellular channel (CLIC) protein, CLIC4, translocates to the nucleus in response to cellular stress, facilitated by a putative CLIC4 nuclear localization signal (NLS). The CLIC4 NLS adopts an alpha-helical structure in the native CLIC4 fold. It is proposed that CLIC4 is transported to the nucleus via the classical nuclear import pathway after binding the import receptor, importin-alpha. In this study, we have determined the X-ray crystal structure of a truncated form of importin-alpha lacking the importin-beta binding domain, bound to a CLIC4 NLS peptide. The NLS peptide binds to the major binding site in an extended conformation similar to that observed for the classical simian virus 40 large T-antigen NLS. A Tyr residue within the CLIC4 NLS makes surprisingly favourable interactions by forming side-chain hydrogen bonds to the importin-alpha backbone. This structural evidence supports the hypothesis that CLIC4 translocation to the nucleus is governed by the importin-alpha nuclear import pathway, provided that CLIC4 can undergo a conformational rearrangement that exposes the NLS in an extended conformation.
PDB ID: 3OQSDownload
MMDB ID: 93158
PDB Deposition Date: 2010/9/3
Updated in MMDB: 2011/08
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Mus musculus
Similar Structures:
Biological Unit for 3OQS: dimeric; determined by author and by software (PISA)
Molecular Components in 3OQS
Label Count Molecule
Proteins (2 molecules)
1
Peptide of Chloride Intracellular Channel Protein 4(Gene symbol: CLIC4)
Molecule annotation
1
Importin Subunit Alpha-2(Gene symbol: Kpna2)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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