Regulator G protein signalizacije
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| Struktura aktivnih konformacija Gi alfa 1.[1] | |||||||||
| Identifikatori | |||||||||
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| Simbol | RGS | ||||||||
| Pfam | PF00615 | ||||||||
| InterPro | IPR000342 | ||||||||
| SMART | RGS | ||||||||
| PROSITE | PDOC50132 | ||||||||
| SCOP | 1gia | ||||||||
| Superfamilija | 1gia | ||||||||
| OPM protein | 2bcj | ||||||||
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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.
Sledeći ljudski proteini sadrže ovaj domen:
- ADRBK1, ADRBK2, AXIN1, AXIN2
- GRK1, GRK4, GRK5, GRK6, GRK7,
- RGS1, RGS2, RGS3, RGS4, RGS5, RGS6, RGS7, RGS8, RGS9, RGS10, RGS11, RGS12, RGS13, RGS14, RGS16, RGS17, RGS18, RGS19, RGS20, RGS21
- RK
- SNX13
- ↑ 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.
- ↑ 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.
- 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.