Receptor Activation Upon Agonist Binding

This section briefly reviews the models currently applied to describe GPCRs modus operandi. Attempts are made to draw a picture of the molecular events that occur upon agonist binding that lead to G protein activation. The role of palmitoylation is discussed. Finally, modulation of the interactions with intracellular partners is envisaged in the light of the receptor susceptibility to adopt multiconformational states. 5.1. Ternary Complex Models of Receptor Activation In the original ternary...

Different Classes Of Heterotrimeric G Proteins And Their Coupling Properties

The different classes of G proteins are defined by their sequence identity as well as their downstream effector coupling specificity. There are over 20 Ga-subunits known to date, and they are divided into four major Ga subfamilies. Because the coupling of the receptor to the different classes of G proteins specifies the signaling pathways that are activated, GPCRs are functionally classified according to their coupling specificity, such as Gs- or Gq-coupled receptors. Several recent reviews...

References

Palczewski K, Kumasaka T, Hori T, et al. Crystal structure of rhodopsin a G protein-coupled receptor. Science 2000 289 739-745. 2. Trabanino RJ, Hall SE, Vaidehi N, Floriano WB, Kam VWT, Goddard WA 3rd. First principles predictions of the structure and function of G-protein-coupled receptors validation for bovine rhodopsin. Biophys J 2004 86 1904-1921. 3. Wallin E, von Heijne G. Properties of N-terminal tails in G-protein coupled receptors a statistical study. Protein Eng 1995 8 693-698. 4....

Biosynthesis Of Oligomers Of Gpcrs

Intracellular Formation of GPCR Oligomers The study of specific GPCR mutants, both naturally occurring and genetically modified, has provided a useful tool in locating the intracellular site of GPCR oligomer formation 24-29 . An increasing number of reports demonstrate that co-expression of various intracellularly sequestered GPCR mutants with the corresponding wild-type receptors results in intracellular retention of the wild-type receptor. These dominant negative effects are a...

Neuronal Regulation Heterotrimeric G Protein Pathways And Neuronal Plasticity

Neurite outgrowth is an important process by which neurons achieve neuronal connectivity during brain development. The mechanism involved in this process requires coordination of signals coming from outside and inside the cell. The growth cone is a critical structure in the neuron that is important for such function. The nerve growth cone is the motile structure at the tip of elongating axons and dendrites and is believed to be responsible for recognizing pathways and targets and transducing...

Advantages And Limitations Of Biochemical And Biophysical Approaches

The oligomerization of GPCRs has been studied using many different approaches. Biochemical and biophysical approaches both have provided strong evidence to support the existence of GPCR dimers or oligomers. However, the different methodologies have advantages and disadvantages that need to be considered when deciding which technique is to be used in the investigation of receptor-receptor interactions and also when interpreting the findings obtained from applying different approaches....