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

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

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

Nat Commun. 2017 Feb 22;8:14523

Authors: Toyama Y, Kano H, Mase Y, Yokogawa M, Osawa M, Shimada I

Abstract
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 ?-subunit (G?) 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 G? on a microsecond timescale. We show that G? 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.


PMID: 28223697 [PubMed - in process]



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