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

Fingerprint

Karyopherins
Nuclear Envelope
Mutant Proteins
Chromosome Segregation
Mutation
Spindle Apparatus
Cell Nucleus Active Transport
Interphase
Nuclear Proteins
Mitosis
Drosophila
Spectrum Analysis
Peptides
Genes
Proteins

Keywords

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

Cite this

Timinszky, G., Tirián, L., Nagy, F. T., Tóth, G., Perczel, A., Kiss-László, Z., ... Szabad, J. (2002). The importin-β P446L dominant-negative mutant protein loses RanGTP binding ability and blocks the formation of intact nuclear envelope. Journal of Cell Science, 115(8), 1675-1687.
Timinszky, Gyula ; Tirián, László ; Nagy, Ferenc T. ; Tóth, Gábor ; Perczel, András ; Kiss-László, Zsuzsanna ; Boros, Imre ; Clarke, Paul R. ; Szabad, János. / The importin-β P446L dominant-negative mutant protein loses RanGTP binding ability and blocks the formation of intact nuclear envelope. In: Journal of Cell Science. 2002 ; Vol. 115, No. 8. pp. 1675-1687.
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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.",
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Timinszky, G, Tirián, L, Nagy, FT, Tóth, G, Perczel, A, Kiss-László, Z, Boros, I, Clarke, PR & Szabad, J 2002, 'The importin-β P446L dominant-negative mutant protein loses RanGTP binding ability and blocks the formation of intact nuclear envelope', Journal of Cell Science, vol. 115, no. 8, pp. 1675-1687.

The importin-β P446L dominant-negative mutant protein loses RanGTP binding ability and blocks the formation of intact nuclear envelope. / Timinszky, Gyula; Tirián, László; Nagy, Ferenc T.; Tóth, Gábor; Perczel, András; Kiss-László, Zsuzsanna; Boros, Imre; Clarke, Paul R.; Szabad, János (Lead / Corresponding author).

In: Journal of Cell Science, Vol. 115, No. 8, 15.05.2002, p. 1675-1687.

Research output: Contribution to journalArticle

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AU - Nagy, Ferenc T.

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AU - Perczel, András

AU - Kiss-László, Zsuzsanna

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AU - Clarke, Paul R.

AU - Szabad, János

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AB - 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.

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Timinszky G, Tirián L, Nagy FT, Tóth G, Perczel A, Kiss-László Z et al. The importin-β P446L dominant-negative mutant protein loses RanGTP binding ability and blocks the formation of intact nuclear envelope. Journal of Cell Science. 2002 May 15;115(8):1675-1687.