Crystal structure of a GA protein βγdimer at 2.1 Å resolution

  title={Crystal structure of a GA protein $\beta$$\gamma$dimer at 2.1 {\AA} resolution},
  author={John Sondek and Andrew Bohm and David G. Lambright and Heidi E. Hamm and Paul B. Sigler},
MANY signalling cascades use seven-helical transmembrane receptors coupled to heterotrimeric G proteins (Gαβγ) to convert extracellular signals into intracellular responses1. Upon nucleotide exchange catalysed by activated receptors, heterotrimers dissociate into GTP-bound Gα subunits and Gβγ dimers, either of which can modulate many downstream effectors2,3. Here we use multiwavelength anomalous diffraction data to solve the crystal structure of the βγ dimer of the G protein transducin. The… 

Understanding Molecular Recognition by G protein βγ Subunits on the Path to Pharmacological Targeting

Evidence has accumulated that one mechanism for Gβγ multitarget recognition is through an intrinsically flexible protein surface or "hot spot" that accommodates multiple modes of binding, which suggests that these interactions could be selectively manipulated with small molecules, which could have significant therapeutic potential.

Structural Determinants for Interaction with Three Different Effectors on the G Protein β Subunit*

It is suggested that the proper folding of the first five β strands in the G protein β subunit is a requirement for appropriately positioning residues that interact with GIRK1 and PLC-β2.

Crystal structure of the multifunctional Gβ5–RGS9 complex

This structure reveals a canonical RGS domain that is functionally integrated within a molecular complex that is poised for integration of multiple steps during G-protein activation and deactivation.

Mutant G protein α subunit activated by Gβγ: A model for receptor activation?

It is concluded that βγ can activate βs and that this effect probably involves both a tilt of βγ relative to αs and interaction of β with the lip of the nucleotide binding pocket.



Structural and functional relationships of heterotrimeric G‐proteins

  • S. Rens‐DomianoH. Hamm
  • Biology, Chemistry
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 1995
The structural features of G‐proteins are discussed, as well as the mechanism by which G‐ Proteins interact with receptors and effectors are detailed.

The 2.0 Å crystal structure of a heterotrimeric G protein

The structure of a heterotrimeric G protein reveals the mechanism of the nucleotide-dependent engagement of the α and βγ subunits that regulates their interaction with receptor and effector

Identification of a Discrete Region of the G Protein γ Subunit Conferring Selectivity in βγ Complex Formation (*)

The identification of multiple G protein β and γ subunit subtypes suggests a potential diversity of βγ heterodimers, which may contribute to the specificity of signal transduction between receptors

New roles for G-protein (βγ-dimers in transmembrane signalling

New evidence indicates that the Gβγ dimer also plays a major part in signal transmission, enhancing the complexity of the possible interactions between the G proteins and their targets.

Repetitive segmental structure of the transducin beta subunit: homology with the CDC4 gene and identification of related mRNAs.

  • H. FongJ. Hurley M. Simon
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1986
The results suggest that the mRNAs in retina are the processed products of a small number of closely related genes or of a single highly complex beta gene.

Selectivity in signal transduction determined by gamma subunits of heterotrimeric G proteins.

Particular alpha and beta subunit subtypes participate in the signal transduction processes between somatostatin or muscarinic receptors and the voltage-sensitive L-type calcium channel in rat pituitary GH3 cells.

A segment of the C-terminal half of the G-protein beta 1 subunit specifies its interaction with the gamma 1 subunit.

  • A. KatzM. Simon
  • Biology, Computer Science
    Proceedings of the National Academy of Sciences of the United States of America
  • 1995
The evidence demonstrates that a chimera between beta 2 and beta 1 that contains the C-terminal 173 amino acids of beta 1 can interact and activate PI-PLC-beta 2 with gamma 1.

Biochemical and genetic analysis of dominant-negative mutations affecting a yeast G-protein gamma subunit.

Because mutant G gamma subunits blocked the constitutive signal resulting from disruption of the G alpha subunit gene (GPA1), they are defective in functions required for downstream signalling.