G protein

G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their activity is regulated by factors that control their ability to bind to and hydrolyze guanosine triphosphate (GTP) to guanosine diphosphate (GDP). When they are bound to GTP, they are 'on', and, when they are bound to GDP, they are 'off'. G proteins belong to the larger group of enzymes called GTPases.

There are two classes of G proteins. The first function as

Heterotrimeric G proteins located within the cell are activated by

• The 1947
  Carl Cori, Gerty Cori and Bernardo Houssay, for their discovery of how glycogen is broken down to glucose and resynthesized in the body, for use as a store and source of energy. Glycogenolysis is stimulated by numerous hormones and neurotransmitters including adrenaline
  .
• The 1970 Nobel Prize in Physiology or Medicine to Julius Axelrod, Bernard Katz and Ulf von Euler for their work on the release and reuptake of neurotransmitters.
• The 1971
  cyclic AMP.^[9]
• The 1988
  Gertrude Elion
  "for their discoveries of important principles for drug treatment" targeting GPCRs.
• The 1992 Nobel Prize in Physiology or Medicine to Edwin G. Krebs and Edmond H. Fischer for describing how reversible phosphorylation works as a switch to activate proteins, and to regulate various cellular processes including glycogenolysis.^[11]
• The 1994 Nobel Prize in Physiology or Medicine to Alfred G. Gilman and Martin Rodbell for their discovery of "G-proteins and the role of these proteins in signal transduction in cells".^[12]
• The 2000 Nobel Prize in Physiology or Medicine to Eric Kandel, Arvid Carlsson and Paul Greengard, for research on neurotransmitters such as dopamine, which act via GPCRs.
• The 2004 Nobel Prize in Physiology or Medicine to Richard Axel and Linda B. Buck for their work on G protein-coupled olfactory receptors.^[13]
• The 2012 Nobel Prize in Chemistry to Brian Kobilka and Robert Lefkowitz for their work on GPCR function.^[14]

Function

G proteins are important

All eukaryotes use G proteins for signaling and have evolved a large diversity of G proteins. For instance, humans encode 18 different G_α proteins, 5 G_β proteins, and 12 G_γ proteins.^[17]

Signaling

G protein can refer to two distinct families of proteins.

Different types of heterotrimeric G proteins share a common mechanism. They are activated in response to a conformational change in the GPCR, exchanging GDP for GTP, and dissociating in order to activate other proteins in a particular signal transduction pathway.^[18] The specific mechanisms, however, differ between protein types.

Mechanism

Receptor-activated G proteins are bound to the inner surface of the cell membrane. They consist of the G_α and the tightly associated G_βγ subunits. There are four main families of G_α subunits: Gα_s (G stimulatory), Gα_i (G inhibitory), Gα_q/11, and Gα_12/13.^[20][21] They behave differently in the recognition of the effector molecule, but share a similar mechanism of activation.

Activation

When a