Mutation of the highly conserved Arg165 and Glu168 residues of human Gsα disrupts the αD–αE loop and enhances basal GDP/GTP exchange rate

  title={Mutation of the highly conserved Arg165 and Glu168 residues of human Gs$\alpha$ disrupts the $\alpha$D–$\alpha$E loop and enhances basal GDP/GTP exchange rate},
  author={Mar{\'i}a Victoria Hinrichs and Mart{\'i}n A. Montecino and Marta Bunster and Juan Olate},
  journal={Journal of Cellular Biochemistry},
G protein signalling regulates a wide range of cellular processes such as motility, differentiation, secretion, neurotransmission, and cell division. G proteins consist of three subunits organized as a Gα monomer associated with a Gβγ heterodimer. Structural studies have shown that Gα subunits are constituted by two domains: a Ras‐like domain, also called the GTPase domain (GTPaseD), and an helical domain (HD), which is unique to heterotrimeric G‐proteins. The HD display significantly higher… 
A positive genotype–phenotype correlation in a large cohort of patients with Pseudohypoparathyroidism Type Ia and Pseudo-pseudohypoparathyroidism and 33 newly identified mutations in the GNAS gene
In the largest cohort of PHPIa and PPHP patients described to date, the spectrum of known GNAS mutations and hot spots is extended and a correlation between the genetic defects and the expression of a clinical AHO‐feature is demonstrated for the first time.
Reduced levels of the adenomatous polyposis coli (APC) protein are associated with ceramide-induced apoptosis of colon cancer cells
The findings indicate that C2-ceramide can induce apoptosis independently of the p53/p21(Waf-1/Cip-1) pathway and that the reduction in the levels of this protein plays a key role in the ability of C2 -ceramide to induced apoptosis of colon cancer cells.
Visualizing G protein signaling in living cells
This dissertation aims to provide a history of web exceptionalism from 1989 to 2002, a period chosen in order to explore its roots as well as specific cases up to and including the year in which descriptions of “Web 2.0” began to circulate.


S111N mutation in the helical domain of human Gsα reduces its GDP/GTP exchange rate
It is demonstrated that the recombinant S111N Gsα was functional since it was able to undergo the characteristic conformational change upon GTP binding, detected by the acquisition of a trypsin‐resistant conformation, which provides new evidence that involves the HD as a regulator of Gs α function, in this case the αA helix, which is not directly involved with the nucleotide binding site nor the interdomain interface.
Mutagenesis in the switch IV of the helical domain of the human Gsα reduces its GDP/GTP exchange rate
Two human Gsα mutant proteins are constructed in which four and five switch IV residues are changed for the ones present in the Xenopus protein, providing new evidence on the role that HD is playing in modulating the GDP/GTP exchange of the Gs α subunit.
The NH2‐terminal α subunit attenuator domain confers regulation of G protein activation by βγ complexes
The findings are consistent with previous observation that a region in the NH2‐terminal moiety functions as an attenuator domain controlling GDP dissociation and GTP activation of the α subunit polypeptide and that the attenuATOR domain is involved in functional recognition and regulation by βγ complexes.
Mechanism of Allosteric Regulation of the Rod cGMP Phosphodiesterase Activity by the Helical Domain of Transducin α Subunit*
The data suggest the that Gαt-HDt regulates PDE by allosterically decreasing the affinity of Pαβ for Pγ and thus simultaneously facilitating the interaction of the activated G αt-Ras-like domain with Pγ.
The α-Helical Domain of Gαt Determines Specific Interaction with Regulator of G Protein Signaling 9*
A distinct, nonoverlapping pattern of RGS and Pγ interaction with Gαt suggests a unique mechanism of effector-mediated GAP function of the RGS9.
Structures of active conformations of Gi alpha 1 and the mechanism of GTP hydrolysis.
AlF4- complexes formed by the G protein Gi alpha 1 demonstrate specific roles in transition-state stabilization for two highly conserved residues, suggesting a mechanism that may promote release of the beta gamma subunit complex when the alpha subunit is activated by GTP.
Mutations at the Domain Interface of Gsα Impair Receptor-mediated Activation by Altering Receptor and Guanine Nucleotide Binding*
The results suggest that interactions between residues across the domain interface are involved in two key steps of receptor-mediated activation, promotion of GTP binding and subsequent receptor-G protein dissociation.
The Function of Interdomain Interactions in Controlling Nucleotide Exchange Rates in Transducin*
It is found that opening of the interdomain cleft is not an energetic barrier to nucleotide exchange in Gαt, and experiments with Gαi1 suggest by comparison that the organization and function of the Interdomain region differ among various G protein subtypes.
G protein mechanisms: insights from structural analysis.
  • S. Sprang
  • Biology, Chemistry
    Annual review of biochemistry
  • 1997
This review is concerned with the structures and mechanisms of a superfamily of regulatory GTP hydrolases (G proteins). G proteins include Ras and its close homologs, translation elongation factors,