Heterotrimeric G protein

Heterotrimeric G protein

[
http://www.pdb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb58_1.html more details...] )] "G protein" usually refers to the membrane-associated heterotrimeric G proteins, sometimes referred to as the "large" G proteins". These proteins are activated by G protein-coupled receptors and are made up of alpha (α), beta (β) and gamma (γ) subunits.cite journal |author=Hurowitz EH, Melnyk JM, Chen YJ, Kouros-Mehr H, Simon MI, Shizuya H|title=Genomic characterization of the human heterotrimeric G protein alpha, beta, and gamma subunit genes|journal=DNA Res |volume= 7 |issue= 2 |pages= 111–20 |year= 2000| doi =10.1093/dnares/7.2.111 |pmid= 10819326]

Alpha subunits

Gα subunits consist of two domains, the GTPase domain, and the alpha-helical domain. There exist at least 20 different Gα subunits, which are separated into four main families. This nomenclature is based on their sequence homologies:cite journal | author = Strathmann MP, Simon MI | title = G alpha 12 and G alpha 13 subunits define a fourth class of G protein alpha subunits | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 88 | issue = 13 | pages = 5582–6 | year = 1991 | pmid = 1905812 | doi = 10.1073/pnas.88.13.5582 | issn = ]

*Gαs or simply Gs (stimulatory) - activates adenylate cyclase to increase cAMP synthesis. This family consist of Gαs and Golf (olfactory) - couples to olfactory receptors
** GNAL
** gene|GNAS
*Gαi or simply Gi (inhibitory) - inhibits adenylate cyclase. This family consist of Gαi1-3, Gαz, Gαo1/2("o" represent other) and Gαt1/2 (transducin) - transduces visual signals in conjunction with rhodopsin in the retina.
**GNAI1, GNAI2, gene|GNAI3, GNAZ, GNAO1**GNAT1, GNAT2, GNAT3
*Gq - stimulates phospholipase C. Gα11, Gα14, and Gα16 also belongs to this family.
**GNAQ, GNA11, gene|GNA14, gene|GNA15
*The G12/13 family - important for regulating (via guanine nucleotide exchange factors) the cytoskeleton, cell junctions, and other processes related to movements
**gene|GNA12, gene|GNA13

Beta-gamma complex

The β and γ subunits are closely bound to one another and are referred to as the "beta-gamma complex". The Gβγ complex is released from the Gα subunit after its GDP-GTP exchange.

Function

The free Gβγ complex can act as a signaling molecule itself, by activating other second messengers or by gating ion channels directly.

For example, the Gβγ complex, when bound to histamine receptors, can activate phospholipase A2. Gβγ complexes bound to muscarinic acetylcholine receptors, on the other hand, directly open G-protein coupled inward rectifying potassium channels (GIRKs). They can also activate L-type calcium channels, as in H3 receptor pharmacology.

Genes

* Gβ genes: GNB1, GNB2, GNB3, GNB4, GNB5, gene|GNB1L, GNB2L1

* Gγ genes: GNGT1, GNGT2, GNG2, GNG3, GNG4, GNG5, GNG7, gene|GNG8, gene|GNG10, GNG11, GNG12, GNG13

References

External links

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