This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
3oqs
From Proteopedia
Crystal structure of importin-alpha bound to a CLIC4 NLS peptide
Structural highlights
FunctionCLIC4_HUMAN Can insert into membranes and form poorly selective ion channels that may also transport chloride ions. Channel activity depends on the pH. Membrane insertion seems to be redox-regulated and may occur only under oxydizing conditions. Promotes cell-surface expression of HRH3. Has alternate cellular functions like a potential role in angiogenesis or in maintaining apical-basolateral membrane polarity during mitosis and cytokinesis. Could also promote endothelial cell proliferation and regulate endothelial morphogenesis (tubulogenesis).[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedIt 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 alpha-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-alpha. In this study, we have determined the X-ray crystal structure of a truncated form of importin-alpha lacking the importin-beta 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-alpha backbone. This structural evidence supports the hypothesis that CLIC4 translocation to the nucleus is governed by the importin-alpha nuclear import pathway, provided that CLIC4 can undergo a conformational rearrangement that exposes the NLS in an extended conformation. Crystal structure of importin-alpha bound to a peptide bearing the nuclear localisation signal from chloride intracellular channel protein 4.,Mynott AV, Harrop SJ, Brown LJ, Breit SN, Kobe B, Curmi PM FEBS J. 2011 May;278(10):1662-75. doi: 10.1111/j.1742-4658.2011.08086.x., Epub 2011 Mar 30. PMID:21388519[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||
