The importin-β P446L dominant-negative mutant protein loses RanGTP binding ability and blocks the formation of intact nuclear envelope

Gyula Timinszky, László Tirián, Ferenc T. Nagy, Gábor Tóth, András Perczel, Zsuzsanna Kiss-László, Imre Boros, Paul R. Clarke, János Szabad (Lead / Corresponding author)

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Three of the four independently induced KetelD dominant-negative female sterile mutations that identify the Drosophila importin-β gene, originated from a C4114→T transition and the concurrent replacement of Pro446 by Leu (P446L). CD spectroscopy of representative peptides with Pro or Leu in the crucial position revealed that upon the Pro→Leu exchange the P446L mutant protein loses flexibility and attains most likely an open conformation. The P446L mutation abolishes RanGTP binding of the P446L mutant form of importin-β protein and results in increased RanGDP binding ability. Notably, the P446L mutant importin-β does not exert its dominant-negative effect on nuclear protein import and has no effect on mitotic spindle-related functions and chromosome segregation. However, it interferes with nuclear envelope formation during mitosis-to-interphase transition, revealing a novel function of importin-β.

Original languageEnglish
Pages (from-to)1675-1687
Number of pages13
JournalJournal of Cell Science
Volume115
Issue number8
Publication statusPublished - 15 May 2002

Keywords

  • Dominant-negative mutations
  • Drosophila
  • Importin-β
  • Nuclear envelope formation
  • Ran

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