Crystal structure of importin-α bound to a peptide bearing the nuclear localisation signal from chloride intracellular channel protein 4

Andrew V. Mynott, Stephen J. Harrop, Louise J. Brown, Samuel N. Breit, Bostjan Kobe, Paul M G Curmi

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

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. Database âStructural data are available in the protein Data Bank under the accession number 30QS. Structured digital abstract and by The X-ray crystal structure of importin-α bound to a human chloride intracellular channel (CLIC4) nuclear localization signal (NLS) peptide has been determined. The NLS peptide binds to the major binding site in an extended conformation. This structural evidence supports the hypothesis that CLIC4 translocation to the nucleus is governed by the importin-α nuclear import pathway, providing CLIC4 can undergo a conformational rearrangement to expose the NLS

Original languageEnglish
Pages (from-to)1662-1675
Number of pages14
JournalFEBS Journal
Volume278
Issue number10
DOIs
Publication statusPublished - May 2011

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