G-proteins

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Guanine nucleotide binding protein binds GTP when activated, which it hydrolyses to GDP. G-proteins are a form trimeric proteins, meaning they have 3 subunits, Alpha, Beta and Gamma. The trimeric protein is activated by the displacement of GDP with GTP through a conformation change in the receptor to which the G-protein is coupled, which in turn causes the release of the alpha subunit (Gsα). The active form of the protein can interact with a number of downstream effectors such as adenylyl cyclase (producing cAMP from ATP), and phospholipase C (PLC).

G-proteins can be divided into two families - the heterotrimeric G-proteins and the small or mono-meric G-proteins, which are mainly involved with enzyme-linked receptors[1].

G-protein coupled receptors (GPCRs) upon binding of a stimulus (in the form of a signalling ligand molecule) activate their coupled G-protein.

The structure of a GPCR is of a serpentine receptor, with 7 transmembrane spans, with 3 exoloops and 4 cytoloops. The N-terminal is found on the extracellular side of the membrane and the C-terminal found on the cytosolic side of the membrane.

Contents

G protein families

There are 4 major families of heterotrimeric G-protein. G-proteins are divided based on the homology of their alpha subunit. Each receptor only affects one type of G-protein[2].

There are 20 alpha subunits, 6 beta subunits and 12 gamma subunits in human that make up the diversity of G-proteins.

Heterotrimeric G-proteins contain three subunits: alpha, beta and gamma. In the inactive form, all three subunits are associated together and GDP binds to the alpha subunit and the alpha and gamma subunits are covalently bonded to lipid molecules in the membrane[3]. On activation, there is a conformational change in the alpha subunit, which now binds to GTP and dissociates from the beta-gamma complex. The alpha subunit and beta-gamma complex can now interact with different effectors to bring about a response. The GTPase activity of the alpha subunit causes the loss of GTP from the binding site in the alpha subunit, and another GDP binds, resetting the system- GTP is hydrolysed to GDP and an inorganic phosphate, which inactivates the alpha subunit[4]. G-proteins can be classified as either trimeric, which are seen bound to G protein-coupled receptors, or as monomeric (eg the RAS protein), which lack the three different subunits that trimeric G-proteins have[5].

Family I

Consists of Gs and Golf. The alpha subunit mediates the function in both G-proteins. Gs activates adenylyl cyclase and Calcium ion channels while Golf activates adenylyl cyclase in olfactory sensory neurons.

Family II

Consists of Gi, Go and Gt. The alpha subunit of Gi inhibits adenylyl cyclase while the beta-gamma complex of Gi activates potassium ion channels. For Go, the beta-gamma complex activates Potassium ion channels and at the same time inactivates Calcium ion channel. Both alpha subunit and beta-gamma complex of Go activate phospholipase C-beta. The alpha subunit of Gt activates cyclic GMP phosphodiesterase in vertebrate rod photoreceptors.

Family III

Consists of Gq. The alpha subunit of Gq functions to activate phospholipase C-beta.

Family IV

Consists of G12/13. The action of alpha subunit of G12/13 is to activate Rho family monomeric GTPase.

References:

  1. https://courses.washington.edu/conj/bess/gpcr/gpcr.htm
  2. Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Robers and Peter Walter(2008) Molecular Biology of The Cell, 5th edition, USA: Garland Science. pg 919
  3. https://courses.washington.edu/conj/bess/gpcr/gpcr.htm
  4. Alberts et al., Molecular Biology Of The Cell, Fifth Edition
  5. Alberts B, et al. Molecular biology of the cell, 6th ed. New York: Garland Science, Taylor and Francis Group; 2015.
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