Molecular basis for the recognition of phosphorylated STAT1 by importin alpha5.

Journal of Molecular Biology
Jonathan NardozziGino Cingolani

Abstract

Interferon-gamma stimulation triggers tyrosine phosphorylation of the transcription factor STAT1 at position 701, which is associated with switching from carrier-independent nucleocytoplasmic shuttling to carrier-mediated nuclear import. Unlike most substrates that carry a classical nuclear localization signal (NLS) and bind to importin alpha1, STAT1 possesses a nonclassical NLS recognized by the isoform importin alpha5. In the present study, we have analyzed the mechanisms by which importin alpha5 binds phosphorylated STAT1 (pSTAT1). We found that a homodimer of pSTAT1 is recognized by one equivalent of importin alpha5 with K(d)=191+/-20 nM. Whereas tyrosine phosphorylation at position 701 is essential to assemble a pSTAT1-importin alpha5 complex, the phosphate moiety is not a direct binding determinant for importin alpha5. In contrast to classical NLS substrates, pSTAT1 binding to importin alpha5 is not displaced by the N-terminal importin beta binding domain and requires the importin alpha5 C-terminal acidic tail (505-EEDD-508). A local unfolding of importin alpha5 Armadillo (ARM) repeat 10 accompanies high-affinity binding to pSTAT1. This unfolding is mediated by a single conserved tyrosine at position 476 of importin alpha...Continue Reading

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Citations

Mar 3, 2011·The Journal of Biological Chemistry·Adem C Koksal, Gino Cingolani
Dec 2, 2011·The Journal of Biological Chemistry·Ruth A PumroyGino Cingolani
May 18, 2011·Molecular and Cellular Biology·Filipa AntunesUwe Vinkemeier
Dec 25, 2010·Cell Communication and Signaling : CCS·Jonathan D NardozziGino Cingolani
Mar 8, 2012·Nucleic Acids Research·Michelle L AmmermanLaurie K Read
Feb 7, 2015·The Biochemical Journal·Ruth A Pumroy, Gino Cingolani
Sep 24, 2013·JAK-STAT·Remi FagardFanny Baran-Marszak
Jan 21, 2012·Biophysical Journal·Jasmin SpeilUlrich Kubitscheck
Oct 30, 2010·Biochimica Et Biophysica Acta·Kaylen Lott, Gino Cingolani
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Feb 7, 2017·Journal of Biomolecular Structure & Dynamics·Takahide OkuyamaHiroki Kaneko
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Jun 8, 2021·The Journal of Biological Chemistry·Qingtang ShenAlexander F Palazzo

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