Regulator G protein signalizacije

Regulator G protein signalnog domena
Struktura aktivnih konformacija Gi alfa 1.[1]
Identifikatori
Simbol RGS
Pfam PF00615
InterPro IPR000342
SMART RGS
PROSITE PDOC50132
SCOP 1gia
Superfamilija 1gia
OPM protein 2bcj
Dostupne PDB strukture:
Pfam structures
PDB RCSB PDB; PDBe
PDBsum strukturni pregled

Regulatori G protein signalizacije (ili RGS) su proteinski strukturni domeni koji aktiviraju GTPaze za heterotrimerne G-proteinske alfa-podjedinice.

RGS proteini su multi-funkcionalni, ubrzavajući proteini GTPaza, koji podstiču GTP hidrolizu alfa podjedinicama heterotrimernih G proteina, čime inaktiviraju G protein i brzo prekidaju signalni puteve G protein-spregnutih receptora[2]. Nakon aktivacije GPCR receptora, heterotrimerni G proteini razmenjuju GDP za GTP, odvajaju se od receptora, i disociraju se u slobodnu, aktivnu GTP-vezanu alfa podjedinicu i beta-gama dimer, ova od kojih aktiviraju nizvodne efektore. Respons se okončava nakon GTP hidrolize alfa podjedinice (IPR001019), koja se zatim vezuje sa beta-gama dimerom (IPR001632 IPR001770) i receptorom. RGS proteini primetno umanjuju životni vek GTP-vezanih alfa podjedinica i stabilizuju G protein prelazno stanje.

Primeri

Sledeći ljudski proteini sadrže ovaj domen:

Vidi još

Literatura

  1. Coleman DE, Berghuis AM, Lee E, Linder ME, Gilman AG, Sprang SR (September 1994). „Structures of active conformations of Gi alpha 1 and the mechanism of GTP hydrolysis”. Science 265 (5177): 1405–12. DOI:10.1126/science.8073283. PMID 8073283. 
  2. De Vries L, Farquhar MG, Zheng B, Fischer T, Elenko E (2000). „The regulator of G protein signaling family”. Annu. Rev. Pharmacol. Toxicol. 40: 235–271. DOI:10.1146/annurev.pharmtox.40.1.235. PMID 10836135. 

Dodatna literatura

  • Structure of RGS4 bound to AlF4--activated G(i alpha1): stabilization of the transition state for GTP hydrolysis. Tesmer JJ, Berman DM, Gilman AG, Sprang SR; Cell 1997;89:251-261.
  • Tesmer JJ, Berman DM, Gilman AG, Sprang SR (April 1997). „Structure of RGS4 bound to AlF4--activated G(i alpha1): stabilization of the transition state for GTP hydrolysis”. Cell 89 (2): 251–61. PMID 9108480. 
  • Dohlman HG, Apaniesk D, Chen Y, Song J, Nusskern D (July 1995). „Inhibition of G-protein signaling by dominant gain-of-function mutations in Sst2p, a pheromone desensitization factor in Saccharomyces cerevisiae”. Mol. Cell. Biol. 15 (7): 3635–43. PMC 230601. PMID 7791771. 
  • Watson N, Linder ME, Druey KM, Kehrl JH, Blumer KJ (September 1996). „RGS family members: GTPase-activating proteins for heterotrimeric G-protein alpha-subunits”. Nature 383 (6596): 172–5. DOI:10.1038/383172a0. PMID 8774882. 
  • Berman DM, Wilkie TM, Gilman AG (August 1996). „GAIP and RGS4 are GTPase-activating proteins for the Gi subfamily of G protein alpha subunits”. Cell 86 (3): 445–52. PMID 8756726. 
  • De Vries L, Mousli M, Wurmser A, Farquhar MG (December 1995). „GAIP, a protein that specifically interacts with the trimeric G protein G alpha i3, is a member of a protein family with a highly conserved core domain”. Proc. Natl. Acad. Sci. U.S.A. 92 (25): 11916–20. DOI:10.1073/pnas.92.25.11916. PMC 40514. PMID 8524874. 
  • Dohlman HG (October 2009). „RGS proteins: The early days”. Prog Mol Biol Transl Sci. 86: 1-14. PMID 20374711. 

Spoljašnje veze

  • RGS domen[mrtav link]
  • p
  • r
  • u
Aktivirajući protein GTPaze
Monomerni
Heterotrimeni
Regulator G protein signalizacije: RGS1, RGS2, RGS3, RGS4, RGS5, RGS6, RGS7, RGS8, RGS9, RGS10, RGS11, RGS12, RGS13, RGS14, RGS16, RGS17, RGS18, RGS19, RGS20, RGS21
Faktor razmene guanin nukleotida
EIF2B  Son of Sevenless  Ras-GRF1

FGD: FGD1  FGD2  FGD3  FGD4

ALS2  SIL1  IQSEC2
Drugi
B trdu: peptidi (nrpl/grfl/cytl/horl), receptori (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd, signalni putevi (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
  • p
  • r
  • u
Klasa A: Rodopsinu slični
α1 (A, B, D) • α2 (A, B, C) • β1 • β2 • β3
Adenozinski (A1, A2A, A2B, A3) • P2Y (1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14)
(svi osim 5-HT3) 5-HT1 (A, B, D, E, F) • 5-HT2 (A, B, C) • 5-HT (4, 5A, 6, 7)
Drugi
Acetilholin (M1, M2, M3, M4, M5) • Dopamin (D1, D2, D3, D4, D5) • Histamin (H1, H2, H3, H4) • Melatonin (1A, 1B, 1C) • TAAR (1, 2, 3, 5, 6, 8, 9)
Metaboliti i
signalni molekuli
CysLT (1, 2) • LTB4 (1, 2) • FPRL1 • OXE • Prostaglandin (DP (1, 2), EP (1, 2, 3, 4), FP) • Prostaciklin • Tromboksan
Drugi
Žučna kiselina • Kanabinoidni (CB1, CB2, GPR (18, 55, 119)) • EBI2 • Estrogen • Slobodna masna kiselina (1, 2, 3, 4) • Laktat  • Lizofosfatidna kiselina (1, 2, 3, 4, 5, 6)  • Lizofosfolipid (1, 2, 3, 4, 5, 6, 7, 8) • Niacin (1, 2) • Oksoglutarat • PAF • Sfingozin-1-fosfat (1, 2, 3, 4, 5) • Sukcinat
Peptid
B/W (1, 2) • FF (1, 2) • S • Y (1, 2, 4, 5) • Neuromedin (B, U (1, 2)) • Neurotenzin (1, 2)
Drugi
Anafilatoksin (C3a, C5a) • Angiotenzin (1, 2) • Apelin • Bombezin (BRS3, GRPR, NMBR) • Bradikinin (B1, B2) • Hemokin • Holecistokinin (A, B) • Endotelin (A, B) • Formil peptid (1, 2, 3) • FSH • Galanin (1, 2, 3) • GHB receptor • Gonadotropin-oslobađajući hormon (1, 2) • Grelin • Kispeptin • Luteinizirajući hormon/horiogonadotropin • MAS (1, 1L, D, E, F, G, X1, X2, X3, X4) • Melanokortin (1, 2, 3, 4, 5) • MCHR (1, 2) • Motilin • Opioidni (δ, κ, μ, Nociceptin & ζ, ali ne σ) • Oreksin (1, 2) • Oksitocin • Prokineticin (1, 2) • Prolaktin-oslobađajući peptid • Relaksin (1, 2, 3, 4) • Somatostatin (1, 2, 3, 4, 5) • Tahikinin (1, 2, 3) • Tirotropin • Tirotropin-oslobađajući hormon • Urotenzin-II • Vazopresin (1A, 1B, 2)
Razno
GPR (1, 3, 4, 6, 12, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 31, 32, 33, 34, 35, 37, 39, 42, 44, 45, 50, 52, 55, 61, 62, 63, 65, 68, 75, 77, 78, 81, 82, 83, 84, 85, 87, 88, 92, 101, 103, 109A, 109B, 119, 120, 132, 135, 137B, 139, 141, 142, 146, 148, 149, 150, 151, 152, 153, 160, 161, 162, 171, 173, 174, 176, 177, 182, 183)
Drugi
Adrenomedulin • Mirisni • Opsin (3, 4, 5, 1LW, 1MW, 1SW, RGR, RRH) • Proteazom-aktivirani (1, 2, 3, 4) • SREB (1, 2, 3)
Klasa B: Sekretinu slični
GPR (56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 155, 157)
Drugi
Klasa C: Metabotropni
glutamat / feromon
TAS1R (1, 2, 3) • TAS2R (1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 19, 20, 30, 31, 38, 39, 40, 41, 42, 43, 45, 46, 50)
Drugi
Klasa F:
Frizzled / Zaglađeni
Uvojiti
Frizzled (1, 2, 3, 4, 5, 6, 7, 8, 9, 10)
Zaglađeni
B trdu: peptidi (nrpl/grfl/cytl/horl), receptori (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd, signalni putevi (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)