Membrane interactions of G proteins and other related proteins.

Abstract

Guanine nucleotide-binding proteins, G proteins, propagate incoming messages from receptors to effector proteins. They switch from an inactive to active state by exchanging a GDP molecule for GTP, and they return to the inactive form by hydrolyzing GTP to GDP. Small monomeric G proteins, such as Ras, are involved in controlling cell proliferation, differentiation and apoptosis, and they interact with membranes through isoprenyl moieties, fatty acyl moieties, and electrostatic interactions. This protein-lipid binding facilitates productive encounters of Ras and Raf proteins in defined membrane regions, so that signals can subsequently proceed through MEK and ERK kinases, which constitute the canonical MAP kinase signaling cassette. On the other hand, heterotrimeric G proteins undergo co/post-translational modifications in the alpha (myristic and/or palmitic acid) and the gamma (farnesol or geranylgeraniol) subunits. These modifications not only assist the G protein to localize to the membrane but they also help distribute the heterotrimer (Galphabetagamma) and the subunits generated upon activation (Galpha and Gbetagamma) to appropriate membrane microdomains. These proteins transduce messages from ubiquitous serpentine receptors, which control important functions such as taste, vision, blood pressure, body weight, cell proliferation, mood, etc. Moreover, the exchange of GDP by GTP is triggered by nucleotide exchange factors. Membrane receptors that activate G proteins can be considered as such, but other cytosolic, membranal or amphitropic proteins can accelerate the rate of G protein exchange or even activate this process in the absence of receptor-mediated activation. These and other protein-protein interactions of G proteins with other signaling proteins are regulated by their lipid preferences. Thus, G protein-lipid interactions control the features of messages and cell physiology.

• Authors: Oliver Vögler, Juana M Barceló, Catalina Ribas, Pablo V Escribá
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) 2008 Jul-Aug Vol. 1778 Issue 7-8 Pg. 1640-52 ISSN: 0006-3002 [Print] Netherlands
• PMID: 18402765 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Lipoproteins
• Membrane Proteins
• Receptors, G-Protein-Coupled
• GTP-Binding Proteins
• ras Proteins

Topics

• Amino Acid Sequence
• Animals
• Biophysical Phenomena
• Biophysics
• Cell Membrane (chemistry, metabolism)
• GTP-Binding Proteins (chemistry, genetics, metabolism)
• Genes, ras
• Humans
• Lipoproteins (chemistry, metabolism)
• Membrane Proteins (chemistry, genetics, metabolism)
• Models, Biological
• Molecular Sequence Data
• Molecular Structure
• Mutation
• Receptors, G-Protein-Coupled (chemistry, genetics, metabolism)
• Signal Transduction
• ras Proteins (chemistry, genetics, metabolism)