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Crystal structure of importin‐α bound to a peptide bearing the nuclear localisation signal from chloride intracellular channel protein 4
Author(s) -
Mynott Andrew V.,
Harrop Stephen J.,
Brown Louise J.,
Breit Samuel N.,
Kobe Bostjan,
Curmi Paul M. G.
Publication year - 2011
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2011.08086.x
Subject(s) - importin , nls , nuclear transport , nuclear localization sequence , ran , chemistry , nucleus , biophysics , microbiology and biotechnology , biology , cell nucleus
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 . Structured digital abstract• CLIC4 and importin alpha bind by x‐ray crystallography (View interaction)