ヘテロ三量体Gタンパク質

関: heterotrimeric GTP-binding protein

WordNet

any of a large group of nitrogenous organic compounds that are essential constituents of living cells; consist of polymers of amino acids; essential in the diet of animals for growth and for repair of tissues; can be obtained from meat and eggs and milk and legumes; "a diet high in protein"
a unit of force equal to the force exerted by gravity; used to indicate the force to which a body is subjected when it is accelerated (同)gee, g-force
the 7th letter of the Roman alphabet (同)g

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/11/16 06:36:25」(JST)

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This heterotrimeric G protein is illustrated with its theoretical lipid anchors. GDP is black. Alpha chain is yellow. Beta and gamma chains are blue.

3D structure of a heterotrimeric G protein

"G protein" usually refers to the membrane-associated heterotrimeric G proteins, sometimes referred to as the "large" G proteins (as opposed to the subclass of smaller, monomeric small GTPases) . These proteins are activated by G protein-coupled receptors and are made up of alpha (α), beta (β) and gamma (γ) subunits,^[1] the latter two referred to as the beta-gamma complex.

There are four main families of G proteins: Gi/Go, Gq, Gs, and G12.^[2]

Alpha subunits

Reconstitution experiments carried out in the early 1980s showed that purified G_α subunits can directly activate effector enzymes. The GTP form of the α subunit of transducin (G_t) activates the cyclic GMP phosphodiesterase from retinal rod outer segments,^[3] and the GTP form of the α subunit of the stimulatory G protein (G_s) activates hormone-sensitive adenylate cyclase.^[4]^[5]

G_α subunits consist of two domains, the GTPase domain, and the alpha-helical domain.

There exist at least 20 different G_α subunits, which are separated into four main families. This nomenclature is based on their sequence homologies:^[6]

G-protein-family	α-subunit	Gene	Signal transduction	Use/Receptors (examples)	Effects (examples)
G_i-family
G_i/o	α_i, α_o	GNAO1, GNAI1, GNAI2, GNAI3	Inhibition of adenylate cyclase, opens K⁺-channels (via β/γ subunits), closes Ca²⁺-channels	Muscarinic M₂ and M₄,^[7] chemokine receptors, α₂-Adrenoreceptors, Serotonin 5-HT₁ receptors, Histamine H₃ and H₄, Dopamine D₂-like receptors	Smooth muscle contraction, depress neuronal activity
G_t	α_t (Transducin)	GNAT1, GNAT2	Activation of phosphodiesterase 6	Rhodopsin	Vision
G_gust	α_gust (Gustducin)	GNAT3	Activation of phosphodiesterase 6	Taste receptors	Taste
G_z	α_z	GNAZ	Inhibition of adenylate cyclase	?	Maintaining the ionic balance of perilymphatic and endolymphatic cochlear fluids.
G_s-family
G_s	α_s	GNAS	Activation of adenylate cyclase	Beta-adrenoreceptors; Serotonin 5-HT₄, 5-HT₆ and 5-HT₇; Dopamine D₁-like receptors, Histamine H₂	Increase heart rate, Smooth muscle relaxation, stimulate neuronal activity
G_olf	α_olf	GNAL	Activation of adenylate cyclase	olfactory receptors	Smell
G_q-family
G_q	α_q, α₁₁, α₁₄, α₁₅, α₁₆	GNAQ, GNA11, GNA14, GNA15	Activation of phospholipase C	α₁-Adrenoreceptors, Muscarinic M₁, M₃, and M₅,^[7] Histamine H₁, Serotonin 5-HT₂ receptors	Smooth muscle contraction, Ca²⁺ flux
G_12/13-family
G_12/13	α₁₂, α₁₃	GNA12, GNA13	Activation of the Rho family of GTPases		Cytoskeletal functions, Smooth muscle contraction

Beta-gamma complex

The β and γ subunits are closely bound to one another and are referred to as the beta-gamma complex. Upon activation of the GPCR, the G_βγ complex is released from the G_α subunit after its GDP-GTP exchange.

Function

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

For example, the G_βγ complex, when bound to histamine receptors, can activate phospholipase A₂. G_βγ 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.

References

^ Hurowitz EH, Melnyk JM, Chen YJ, Kouros-Mehr H, Simon MI, Shizuya H; Melnyk; Chen; Kouros-Mehr; Simon; Shizuya (2000). "Genomic characterization of the human heterotrimeric G protein alpha, beta, and gamma subunit genes". DNA Res. 7 (2): 111–20. doi:10.1093/dnares/7.2.111. PMID 10819326.
^ Ellis, Claire (Jul 2004). "The state of GPCR research in 2004". Nature Reviews Drug Discovery (3 ed.). 3 (7): 577–626. doi:10.1038/nrd1458.
^ Fung, BKK; Hurley, JB; Stryer, L (1981). "Flow of information in the light-triggered cyclic nucleotide cascade of vision". Proc. Natl. Acad. Sci. USA. 78 (1): 152–156. doi:10.1073/pnas.78.1.152. PMC 319009. PMID 6264430.
^ Cerione, RA; Sibley, DR; Codina, J; Benovic, JL; Winslow, J; Neer, EJ; Birnbaumer, L; Caron, MG; Lefkowitz, RJ; et al. (1984). "Reconstitution of a hormone-sensitive adenylate cyclase system. The pure beta-adrenergic receptor and guanine nucleotide regulatory protein confer hormone responsiveness on the resolved catalytic unit". J. Biol. Chem. 259 (16): 9979–9982. PMID 6088509.
^ May, DC; Ross, EM; Gilman, AG; Smigel, MD (1985). "Reconstitution of catecholamine-stimulated adenylate cyclase activity using three purified proteins". J. Biol. Chem. 260 (29): 15829–15833. PMID 2999139.
^ Strathmann MP, Simon MI; Simon (1991). "G alpha 12 and G alpha 13 subunits define a fourth class of G protein alpha subunits". Proc. Natl. Acad. Sci. U.S.A. 88 (13): 5582–6. doi:10.1073/pnas.88.13.5582. PMC 51921. PMID 1905812.
^ ^a ^b Kou Qin, Chunmin Dong, Guangyu Wu & Nevin A Lambert; Dong; Wu; Lambert (August 2011). "Inactive-state preassembly of Gq-coupled receptors and Gq heterotrimers". Nature Chemical Biology. 7 (11): 740–747. doi:10.1038/nchembio.642. PMC 3177959. PMID 21873996.

External links

Heterotrimeric G-Proteins at the US National Library of Medicine Medical Subject Headings (MeSH)
EC 3.6.5.1

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English Journal

Quaternary structure of a G-protein-coupled receptor heterotetramer in complex with Gi and Gs.

Navarro G1,2,3, Cordomí A4, Zelman-Femiak M5,6, Brugarolas M1,2,3, Moreno E1,2,3, Aguinaga D1,2,3, Perez-Benito L4, Cortés A1,2,3, Casadó V1,2,3, Mallol J1,2,3, Canela EI1,2,3, Lluís C1,2,3, Pardo L4, García-Sáez AJ5,6,7, McCormick PJ8,9,10,11, Franco R12,13,14.
BMC biology.BMC Biol.2016 Apr 5;14(1):26. doi: 10.1186/s12915-016-0247-4.
BACKGROUND: G-protein-coupled receptors (GPCRs), in the form of monomers or homodimers that bind heterotrimeric G proteins, are fundamental in the transfer of extracellular stimuli to intracellular signaling pathways. Different GPCRs may also interact to form heteromers that are novel signaling unit
PMID 27048449

Heterotrimeric G-protein shuttling via Gip1 extends the dynamic range of eukaryotic chemotaxis.

Kamimura Y1, Miyanaga Y1, Ueda M2.
Proceedings of the National Academy of Sciences of the United States of America.Proc Natl Acad Sci U S A.2016 Apr 4. pii: 201516767. [Epub ahead of print]
Chemotactic eukaryote cells can sense chemical gradients over a wide range of concentrations via heterotrimeric G-protein signaling; however, the underlying wide-range sensing mechanisms are only partially understood. Here we report that a novel regulator of G proteins, G protein-interacting protein
PMID 27044073

G protein γ subunit 7 induces autophagy and inhibits cell division.

Liu J1,2, Ji X1, Li Z1, Yang X1, Wang W1, Zhang X1.
Oncotarget.Oncotarget.2016 Apr 2. doi: 10.18632/oncotarget.8559. [Epub ahead of print]
GNG7 (G protein γ subunit 7), a subunit of heterotrimeric G protein, is ubiquitously expressed in multiple tissues but is down-regulated in various cancers. Its expression could reduce tumor volume in mice but the mechanism was not clear. Here we show that GNG7 overexpression inhibits cell prolifer
PMID 27056891

Japanese Journal

シグナル伝達の選択的な制御を指向したGPCRの構造生命科学

YAKUGAKU ZASSHI 136(2), 179-184, 2016
NAID 130005121475

2C22 軟骨前駆細胞における静水圧刺激と三量体Gタンパク質の活性化との関連(OS4-2:メカノバイオロジー(2))

バイオエンジニアリング講演会講演論文集 2015(27), 393-394, 2015-01-08
NAID 110009965407

2P184 三量体Gタンパク質と相互作用する新規タンパク質Gip1は走化性における応答濃度範囲を広げる働きをする(12. 細胞生物的課題,ポスター,第52回日本生物物理学会年会(2014年度))

生物物理 54(SUPPLEMENT_1-2), S225, 2014-08-20
NAID 110009932730

「ヘテロ三量体Gタンパク」

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Heterotrimeric G-protein GTPase
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　　[★]

英: [[]]
同: heterotrimeric G-protein
関: [[]]

同: heterotrimeric G-protein

「ヘテロ三量体Gタンパク質」

　　[★]

英: heterotrimeric G-protein
関: ヘテロ三量体GTP結合タンパク質

「heterotrimeric GTP-binding protein」

　　[★]

ヘテロ三量体GTP結合タンパク質

関: heterotrimeric G-protein

「G」

　　[★]

「heterotrimeric」

　　[★]

ヘテロ三量体の、ヘテロトリマーの

関: heterotrimer

「heterotrimer」

　　[★]

ヘテロ三量体、ヘテロトリマー

関: heterotrimeric

「G protein」

　　[★]

同: G proteins

同: G proteins

「Gd」

　　[★]

同: ガドリニウム造影MRI

[Hurowitz_2000-1] Hurowitz EH, Melnyk JM, Chen YJ, Kouros-Mehr H, Simon MI, Shizuya H; Melnyk; Chen; Kouros-Mehr; Simon; Shizuya (2000). "Genomic characterization of the human heterotrimeric G protein alpha, beta, and gamma subunit genes". DNA Res. 7 (2): 111–20. doi:10.1093/dnares/7.2.111. PMID 10819326.

[2] Ellis, Claire (Jul 2004). "The state of GPCR research in 2004". Nature Reviews Drug Discovery (3 ed.). 3 (7): 577–626. doi:10.1038/nrd1458.

[3] Fung, BKK; Hurley, JB; Stryer, L (1981). "Flow of information in the light-triggered cyclic nucleotide cascade of vision". Proc. Natl. Acad. Sci. USA. 78 (1): 152–156. doi:10.1073/pnas.78.1.152. PMC 319009. PMID 6264430.

[4] Cerione, RA; Sibley, DR; Codina, J; Benovic, JL; Winslow, J; Neer, EJ; Birnbaumer, L; Caron, MG; Lefkowitz, RJ; et al. (1984). "Reconstitution of a hormone-sensitive adenylate cyclase system. The pure beta-adrenergic receptor and guanine nucleotide regulatory protein confer hormone responsiveness on the resolved catalytic unit". J. Biol. Chem. 259 (16): 9979–9982. PMID 6088509.

[5] May, DC; Ross, EM; Gilman, AG; Smigel, MD (1985). "Reconstitution of catecholamine-stimulated adenylate cyclase activity using three purified proteins". J. Biol. Chem. 260 (29): 15829–15833. PMID 2999139.

[pmid1905812-6] Strathmann MP, Simon MI; Simon (1991). "G alpha 12 and G alpha 13 subunits define a fourth class of G protein alpha subunits". Proc. Natl. Acad. Sci. U.S.A. 88 (13): 5582–6. doi:10.1073/pnas.88.13.5582. PMC 51921. PMID 1905812.

[Kou_Qin-7] Kou Qin, Chunmin Dong, Guangyu Wu & Nevin A Lambert; Dong; Wu; Lambert (August 2011). "Inactive-state preassembly of Gq-coupled receptors and Gq heterotrimers". Nature Chemical Biology. 7 (11): 740–747. doi:10.1038/nchembio.642. PMC 3177959. PMID 21873996.

v t e Enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list)

リンク元	「ヘテロ三量体Gタンパク」「ヘテロ三量体Gタンパク質」「heterotrimeric GTP-binding protein」
関連記事	「G」「heterotrimeric」「heterotrimer」「G protein」「Gd」

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heterotrimeric G-protein