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

  1. Andrew V. Mynott1,
  2. Stephen J. Harrop1,
  3. Louise J. Brown2,
  4. Samuel N. Breit3,
  5. Bostjan Kobe4,5,
  6. Paul M. G. Curmi1,3

Article first published online: 30 MAR 2011

DOI: 10.1111/j.1742-4658.2011.08086.x

Issue

FEBS Journal

FEBS Journal

Volume 278, Issue 10, pages 1662–1675, May 2011

Additional Information

How to Cite

Mynott, A. V., Harrop, S. J., Brown, L. J., Breit, S. N., Kobe, B. and Curmi, P. M. G. (2011), Crystal structure of importin-α bound to a peptide bearing the nuclear localisation signal from chloride intracellular channel protein 4. FEBS Journal, 278: 1662–1675. doi: 10.1111/j.1742-4658.2011.08086.x

Author Information

  1. 1

     School of Physics, University of New South Wales, Sydney, NSW, Australia

  2. 2

     Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, NSW, Australia

  3. 3

     St Vincent’s Centre for Applied Medical Research, St Vincent’s Hospital and University of New South Wales, Sydney, NSW, Australia

  4. 4

     School of Chemistry and Molecular Biosciences and Centre for Infectious Disease Research, University of Queensland, Brisbane, Qld, Australia

  5. 5

     Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld, Australia

*P. Curmi, School of Physics, University of New South Wales, Sydney, NSW 2052, Australia Fax: +61 2 9385 6060 Tel: +61 2 9385 4552 E-mail: P.Curmi@unsw.edu.au

Publication History

  1. Issue published online: 3 MAY 2011
  2. Article first published online: 30 MAR 2011
  3. Accepted manuscript online: 9 MAR 2011 12:29PM EST
  4. (Received 17 November 2010, revised 31 January 2011, accepted 23 February 2011)

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Keywords:

  • chloride intracellular channel protein;
  • CLIC4;
  • importin-α;
  • nuclear localization signal (NLS);
  • nucleocytoplasmic transport

Graphical Abstract

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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

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 Structural data are available in the protein Data Bank under the accession number 3OQS.

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