Abstract
G protein-coupled receptors (GPCRs) allosterically activate heterotrimeric G proteins and trigger GDP release. Given that there are ∼800 human GPCRs and 16 different Gα genes, this raises the question of whether a universal allosteric mechanism governs Gα activation. Here we show that different GPCRs interact with and activate Gα proteins through a highly conserved mechanism. Comparison of Gα with the small G protein Ras reveals how the evolution of short segments that undergo disorder-to-order transitions can decouple regions important for allosteric activation from receptor binding specificity. This might explain how the GPCR-Gα system diversified rapidly, while conserving the allosteric activation mechanism.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Allosteric Regulation*
-
Animals
-
Binding Sites
-
Computational Biology
-
Conserved Sequence
-
Enzyme Activation
-
Evolution, Molecular*
-
GTP-Binding Protein alpha Subunits / chemistry
-
GTP-Binding Protein alpha Subunits / genetics
-
GTP-Binding Protein alpha Subunits / metabolism*
-
Genetic Engineering
-
Guanosine Diphosphate / metabolism
-
Humans
-
Models, Molecular
-
Mutation
-
Protein Structure, Secondary
-
Protein Structure, Tertiary
-
Receptors, G-Protein-Coupled / chemistry
-
Receptors, G-Protein-Coupled / metabolism*
-
Signal Transduction
-
Substrate Specificity
-
ras Proteins / chemistry
-
ras Proteins / metabolism
Substances
-
GTP-Binding Protein alpha Subunits
-
Receptors, G-Protein-Coupled
-
Guanosine Diphosphate
-
ras Proteins