Dynamic regulation of GDP binding to G proteins revealed by magnetic field-dependent NMR relaxation analyses

Yuki Toyama, Hanaho Kano, Yoko Mase, Mariko Yokogawa, Masanori Osawa, Ichio Shimada

研究成果: Article査読

26 被引用数 (Scopus)

抄録

Heterotrimeric guanine-nucleotide-binding proteins (G proteins) serve as molecular switches in signalling pathways, by coupling the activation of cell surface receptors to intracellular responses. Mutations in the G protein α-subunit (Gα) that accelerate guanosine diphosphate (GDP) dissociation cause hyperactivation of the downstream effector proteins, leading to oncogenesis. However, the structural mechanism of the accelerated GDP dissociation has remained unclear. Here, we use magnetic field-dependent nuclear magnetic resonance relaxation analyses to investigate the structural and dynamic properties of GDP bound Gα on a microsecond timescale. We show that Gα rapidly exchanges between a ground-state conformation, which tightly binds to GDP and an excited conformation with reduced GDP affinity. The oncogenic D150N mutation accelerates GDP dissociation by shifting the equilibrium towards the excited conformation.

本文言語English
論文番号14523
ジャーナルNature communications
8
DOI
出版ステータスPublished - 2017 2月 22

ASJC Scopus subject areas

  • 化学 (全般)
  • 生化学、遺伝学、分子生物学(全般)
  • 物理学および天文学(全般)

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