Journal ArticleDOI
Structures of active conformations of Gi alpha 1 and the mechanism of GTP hydrolysis.
David E. Coleman,Albert M. Berghuis,Ethan Lee,Maurine E. Linder,Alfred G. Gilman,Stephen R. Sprang +5 more
Reads0
Chats0
TLDR
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.Abstract:
Mechanisms of guanosine triphosphate (GTP) hydrolysis by members of the G protein alpha subunit-p21ras superfamily of guanosine triphosphatases have been studied extensively but have not been well understood. High-resolution x-ray structures of the GTP gamma S and GDP.AlF4- complexes formed by the G protein Gi alpha 1 demonstrate specific roles in transition-state stabilization for two highly conserved residues. Glutamine204 (Gln61 in p21ras) stabilizes and orients the hydrolytic water in the trigonal-bipyramidal transition state. Arginine 178 stabilizes the negative charge at the equatorial oxygen atoms of the pentacoordinate phosphate intermediate. Conserved only in the G alpha family, this residue may account for the higher hydrolytic rate of G alpha proteins relative to those of the p21ras family members. The fold of Gi alpha 1 differs from that of the homologous Gt alpha subunit in the conformation of a helix-loop sequence located in the alpha-helical domain that is characteristic of these proteins; this site may participate in effector binding. The amino-terminal 33 residues are disordered in GTP gamma S-Gi alpha 1, suggesting a mechanism that may promote release of the beta gamma subunit complex when the alpha subunit is activated by GTP.read more
Citations
More filters
Journal ArticleDOI
A GTPase-activating protein for the G protein Gα(z). Identification, purification, and mechanism of action
TL;DR: A GTPase-activating protein (GAP) specific for Galphaz was identified in brain, spleen, retina, platelet, C6 glioma cells, and several other tissues and cells and is competitively inhibited by both Galphai1 and Galphao at nanomolar concentrations when they are bound to GTPgammaS but not to GDP.
Journal ArticleDOI
Mapping allosteric connections from the receptor to the nucleotide-binding pocket of heterotrimeric G proteins
TL;DR: The data identify a putative pathway of allosteric changes triggered by receptor binding and suggest elements of a mechanism for receptor-catalyzed nucleotide exchange in the structure of switch I and contiguous sequences.
Journal ArticleDOI
Structural-Functional Features of the Thyrotropin Receptor: A Class A G-Protein-Coupled Receptor at Work.
Gunnar Kleinau,Catherine L. Worth,Annika Kreuchwig,Heike Biebermann,Patrick Marcinkowski,Patrick Scheerer,Gerd Krause +6 more
TL;DR: This review summarizes available knowledge concerning the TSHR protein structure, associated functional aspects, and based on these insights the authors suggest several receptor complex models to understand the molecular activation mechanisms of this receptor comprehensively.
Journal ArticleDOI
Crystal Structure of the Gtr1pGTP-Gtr2pGDP Protein Complex Reveals Large Structural Rearrangements Triggered by GTP-to-GDP Conversion
TL;DR: The structure reveals that GTP-to-GDP conversion on Gtr2p results in a large conformational transition of this subunit, including a large scale rearrangement of a long segment whose corresponding region in RagA is involved in binding to Raptor.
Journal ArticleDOI
Interactions of the α-subunits of heterotrimeric G-proteins with GPCRs, effectors and RGS proteins: A critical review and analysis of interacting surfaces, conformational shifts, structural diversity and electrostatic potentials
TL;DR: The study of Gα interacting surfaces in terms of sequence, structure and electrostatic potential reveals features that may account for the Gα subunit's behavior towards its interacting partners, suggesting electrostatic complementarity may be an important factor in G-protein interactions.
References
More filters
Journal ArticleDOI
PROCHECK: a program to check the stereochemical quality of protein structures
TL;DR: The PROCHECK suite of programs as mentioned in this paper provides a detailed check on the stereochemistry of a protein structure and provides an assessment of the overall quality of the structure as compared with well refined structures of the same resolution.
Journal ArticleDOI
MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures
TL;DR: The MOLSCRIPT program as discussed by the authors produces plots of protein structures using several different kinds of representations, including simple wire models, ball-and-stick models, CPK models and text labels.
Journal ArticleDOI
G proteins: transducers of receptor-generated signals
TL;DR: This paper presents a meta-analysis of G Protein Interactions and its Foundations, which states that G Proteins are Law-Regulated and G Protein-Effector Interactions are Nonvolatile.
Journal ArticleDOI
Free R value: a novel statistical quantity for assessing the accuracy of crystal structures.
TL;DR: In this article, a statistical quantity (RfreeT) is defined to measure the agreement between observed and computed structure factor amplitudes for a 'test' set of reflections that is omitted in the modelling and refinement process.
Journal ArticleDOI
The GTPase superfamily: conserved structure and molecular mechanism
TL;DR: GTPases are conserved molecular switches, built according to a common structural design, and rapidly accruing knowledge of individual GTPases—crystal structures, biochemical properties, or results of molecular genetic experiments—support and generate hypotheses relating structure to function in other members of the diverse family of GTPase.