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

2002; The Company of Biologists; Volume: 115; Issue: 8 Linguagem: Inglês

10.1242/jcs.115.8.1675

1477-9137

Gyula Timinszky, László Tirián, Ferenc Nagy, Gábor K. Tóth, András Perczel, Zsuzsanna Kiss-László, Imre Boros, Paul R. Clarke, János Szabad,

Genomics and Chromatin Dynamics

Three of the four independently induced KetelDdominantnegative 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.