3OQS

Crystal structure of importin-alpha bound to a CLIC4 NLS peptide

Summary for 3OQS

• Entry DOI: 10.2210/pdb3oqs/pdb
• Descriptor: peptide of Chloride intracellular channel protein 4, Importin subunit alpha-2 (3 entities in total)
• Functional Keywords: importin alpha, karyopherin alpha, nuclear localisation signal (nls) recognition, chloride intracellular channel 4, clic4 nls, armadillo repeat, nuclear import, protein transport
• Biological source: Mus musculus (mouse); More
• Cellular location: Cytoplasm, cytoskeleton, centrosome: Q9Y696; Cytoplasm (By similarity): P52293
• Total number of polymer chains: 2
• Total formula weight: 56539.06

Authors

Mynott, A.V.,Brown, L.J.,Harrop, S.J.,Curmi, P.M.G. (deposition date: 2010-09-03, release date: 2011-07-27, Last modification date: 2023-11-01)

Primary citation

Mynott, A.V.,Harrop, S.J.,Brown, L.J.,Breit, S.N.,Kobe, B.,Curmi, P.M.G.
Crystal structure of importin-alpha bound to a peptide bearing the nuclear localisation signal from chloride intracellular channel protein 4
Febs J., 278:1662-1675, 2011

PubMed 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 α-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-α. In this study, we have determined the X-ray crystal structure of a truncated form of importin-α lacking the importin-β 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-α backbone. This structural evidence supports the hypothesis that CLIC4 translocation to the nucleus is governed by the importin-α nuclear import pathway, provided that CLIC4 can undergo a conformational rearrangement that exposes the NLS in an extended conformation.

PubMed: 21388519
DOI: 10.1111/j.1742-4658.2011.08086.x

Experimental method

X-RAY DIFFRACTION (2 Å)