Referenced in: none

Automatically associated channels: ClIC4 , Slo1

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

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

Journal, date & volume: FEBS J., 2011 May , 278, 1662-75

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21388519

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.