$\require{mediawiki-texvc}$

연합인증

연합인증 가입 기관의 연구자들은 소속기관의 인증정보(ID와 암호)를 이용해 다른 대학, 연구기관, 서비스 공급자의 다양한 온라인 자원과 연구 데이터를 이용할 수 있습니다.

이는 여행자가 자국에서 발행 받은 여권으로 세계 각국을 자유롭게 여행할 수 있는 것과 같습니다.

연합인증으로 이용이 가능한 서비스는 NTIS, DataON, Edison, Kafe, Webinar 등이 있습니다.

한번의 인증절차만으로 연합인증 가입 서비스에 추가 로그인 없이 이용이 가능합니다.

다만, 연합인증을 위해서는 최초 1회만 인증 절차가 필요합니다. (회원이 아닐 경우 회원 가입이 필요합니다.)

연합인증 절차는 다음과 같습니다.

최초이용시에는
ScienceON에 로그인 → 연합인증 서비스 접속 → 로그인 (본인 확인 또는 회원가입) → 서비스 이용

그 이후에는
ScienceON 로그인 → 연합인증 서비스 접속 → 서비스 이용

연합인증을 활용하시면 KISTI가 제공하는 다양한 서비스를 편리하게 이용하실 수 있습니다.

Structural Aspects of GPCR-G Protein Coupling 원문보기

Toxicological research, v.29 no.3, 2013년, pp.149 - 155  

Chung, Ka Young (School of Pharmacy, Sungkyunkwan University)

Abstract AI-Helper 아이콘AI-Helper

G protein-coupled receptors (GPCRs) are membrane receptors; approximately 40% of drugs on the market target GPCRs. A precise understanding of the activation mechanism of GPCRs would facilitate the development of more effective and less toxic drugs. Heterotrimeric G proteins are important molecular s...

주제어

AI 본문요약
AI-Helper 아이콘 AI-Helper

* AI 자동 식별 결과로 적합하지 않은 문장이 있을 수 있으니, 이용에 유의하시기 바랍니다.

문제 정의

  • Due to the technical difficulties of obtaining crystals of membrane proteins, however, afewmammalian GPCR structures have been obtained mostly during past 6 years (17), and there is only one crystal structure of the receptor-G protein complex (18). This review will summarize the recent advance in the understanding of the structural aspect of G protein activation by GPCRs.

가설 설정

  • Second, GPCRs do not only act as a monomer but also as oligomers (56-58). What would be the coupling mode between G proteins and oligomerized GPCRs? Would GPCR oligomerization affect the G protein selectivity? Third, recent studies suggested that G proteins can interact with inactive GPCRs as a pre-assembled complex (27,59-62). The preassembly of GPCR-G protein can speed-up the signal transduction and provide G protein selectivity of GPCRs (63).
본문요약 정보가 도움이 되었나요?

참고문헌 (63)

  1. 1 Lundstrom K. An overview on GPCRs and drug discovery: structure-based drug design and structural biology on GPCRs. Methods Mol Biol. (2009) 552 51 66 19513641 

  2. 2 Nikiforovich G.V. Taylor C.M. Marshall G.R. Modeling of the complex between transducin and photoactivated rhodopsin, a prototypical G-protein-coupled receptor. Biochemistry (2007) 46 4734 4744 10.1021/bi700185p 17397191 

  3. 3 Wang X. Kim S.H. Ablonczy Z. Crouch R.K. Knapp D.R. Probing rhodopsin-transducin interactions by surface modification and mass spectrometry. Biochemistry (2004) 43 11153 11162 10.1021/bi049642f 15366925 

  4. 4 Oldham W.M. Hamm H.E. Heterotrimeric G protein activation by G-protein-coupled receptors. Nat. Rev. Mol. Cell Biol. (2008) 9 60 71 10.1038/nrm2299 18043707 

  5. 5 Baltoumas F.A. Theodoropoulou M.C. Hamodrakas S.J. Interactions of the α-subunits of heterotrimeric Gproteins with GPCRs, effectors and RGS proteins: a critical review and analysis of interacting surfaces, conformational shifts, structural diversity and electrostatic potentials. J. Struct. Biol. (2013) 182 209 218 10.1016/j.jsb.2013.03.004 23523730 

  6. 6 Tesmer J.J. The quest to understand heterotrimeric G protein signaling. Nat. Struct. Mol. Biol. (2010) 17 650 652 10.1038/nsmb0610-650 20520658 

  7. 7 Jones J.C. Duffy J.W. Machius M. Temple B.R. Dohlman H.G. Jones A.M. The crystal structure of a self-activating G protein alpha subunit reveals its distinct mechanism of signal initiation. Sci. Signaling (2011) 4 ra8 

  8. 8 Lambright D.G. Sondek J. Bohm A. Skiba N.P. Hamm H.E. Sigler P.B. The 2.0A crystal structure of a heterotrimeric G protein. Nature (1996) 379 311 319 10.1038/379311a0 8552184 

  9. 9 Sondek J. Bohm A. Lambright D.G. Hamm H.E. Sigler P.B. Crystal structure of a G-protein beta gamma dimer at 2.1A resolution. Nature (1996) 379 369 374 10.1038/379369a0 8552196 

  10. 10 Wall M.A. Coleman D.E. Lee E. Iiguez-Lluhi J.A. Posner B.A. Gilman A.G. Sprang S.R. The structure of the G protein heterotrimer Gi alpha 1 beta 1 gamma 2. Cell (1995) 83 1047 1058 10.1016/0092-8674(95)90220-1 8521505 

  11. 11 Lambright D.G. Noel J.P. Hamm H.E. Sigler P.B. Structural determinants for activation of the alpha-subunit of a heterotrimeric G protein. Nature (1994) 369 621 628 10.1038/369621a0 8208289 

  12. 12 Sondek J. Lambright D.G. Noel J.P. Hamm H.E. Sigler P.B. GTPase mechanism of Gproteins from the 1.7-A crystal structure of transducin alpha-GDP-AIF-4. Nature (1994) 372 276 279 10.1038/372276a0 7969474 

  13. 13 Noel J.P. Hamm H.E. Sigler P.B. The 2.2A crystal structure of transducin-alpha complexed with GTP gamma S. Nature (1993) 366 654 663 10.1038/366654a0 8259210 

  14. 14 Sunahara R.K. Tesmer J.J. Gilman A.G. Sprang S.R. Crystal structure of the adenylyl cyclase activator Gsalpha. Science (1997) 278 1943 1947 10.1126/science.278.5345.1943 9395396 

  15. 15 Mixon A.G. Lee M.B. Coleman E. Berghuis D.E. Gilman A.M. Sprang S.R. Tertiary and quaternary structural changes in Gi alpha 1 induced by GTP hydrolysis. Science (1995) 270 954 960 10.1126/science.270.5238.954 7481799 

  16. 16 Coleman D.E. Berghuis A.M. Lee E. Linder M.E. Gilman A.G. Sprang S.R. Structures of active conformations of Gi alpha 1 and the mechanism of GTP hydrolysis. Science (1994) 265 1405 1412 10.1126/science.8073283 8073283 

  17. 17 Venkatakrishnan A.J. Deupi X. Lebon G. Tate C.G. Schertler G.F. Babu M.M. Molecular signatures of G-protein-coupled receptors. Nature (2013) 494 185 194 10.1038/nature11896 23407534 

  18. 18 Rasmussen S.G. DeVree B.T. Zou Y. Kruse A.C. Chung K.Y. Kobilka T.S. Thian F.S. Chae P.S. Pardon E. Calinski D. Mathiesen J.M. Shah S.T. Lyons J.A. Caffrey M. Gellman S.H. Steyaert J. Skiniotis G. Weis W.I. Sunahara R.K. Kobilka B.K. Grystal structure of the β2 adrenergic receptor-Gs protein complex. Nature (2011) 477 549 555 10.1038/nature10361 21772288 

  19. 19 Preininger A.M. Van Eps N. Yu N.J. Medkova M. Hubbell W.L. Hamm H.E. The myristoylated amino terminus of Galpha(i)(1) plays a critical role in the structure and function of Galpha(i)(1) subunits in solution. Biochemistry (2003) 42 7931 7941 10.1021/bi0345438 12834345 

  20. 20 Franco M. Chardin P. Chabre M. Paris S. Myristoylation-facilitated binding of the G protein ARF1GDP to membrane phospholipids is required for its activation by a soluble nucleotide exchange factor. J. Biol. Chem. (1996) 271 1573 1578 10.1074/jbc.271.3.1573 8576155 

  21. 21 Degtyarev M.Y. Spiegel A.M. Jones T.L. Palmitoylation of a G protein alpha i subunit requires membrane localization not myristoylation. J. Biol. Chem. (1994) 269 30898 30903 7983022 

  22. 22 Hamm H.E. Deretic D. Arendt A. Hargrave P.A. Koenig B. Hofmann K.P. Site of G protein binding to rhodopsin mapped with synthetic peptides from the alpha subunit. Science (1988) 241 832 835 10.1126/science.3136547 3136547 

  23. 23 Feldman D.S. Zamah A.M. Pierce K.L. Miller W.E. Kelly F. Rapacciuolo A. Rockman H.A. Koch W.J. Luttrell L.M. Selective inhibition of heterotrimeric Gs signaling. Targeting the receptor-G protein interface using a peptide minigene encoding the Galpha(s) carboxyl terminus. J. Biol. Chem. (2002) 277 28631 28640 10.1074/jbc.M204753200 12036966 

  24. 24 Aris L. Gilchrist A. Rens-Domiano S. Meyer C. Schatz P.J. Dratz E.A. Hamm H.E. Structural requirements for the stabilization of metarhodopsin II by the C terminus of the alpha subunit of transducin. J. Biol. Chem. (2001) 276 2333 2339 10.1074/jbc.M002533200 11018024 

  25. 25 Schwindinger W.F. Miric A. Zimmerman D. Levine M.A. A novel Gs alpha mutant in a patient with Albright hereditary osteodystrophy uncouples cell surface receptors from adenylyl cyclase. J. Biol. Chem. (1994) 269 25387 25391 7523385 

  26. 26 Natochin M. Muradov K.G. McEntaffer R.L. Artemyev N.O. Rhodopsin recognition by mutant G(s)alpha containing C-terminal residues of transducin. J. Biol. Chem. (2000) 275 2669 2675 10.1074/jbc.275.4.2669 10644728 

  27. 27 Hu J. Wang Y. Zhang X. Lloyd J.R. Li J.H. Karpiak J. Costanzi S. Wess J. Structural basis of G proteincoupled receptor-G protein interactions. Nat. Chem. Biol. (2010) 6 541 548 10.1038/nchembio.385 20512139 

  28. 28 Cai K. Itoh Y. Khorana H.G. Mapping of contact sites in complex formation between transducin and lightactivated rhodopsin by covalent crosslinking: use of a photoactivatable reagent. Proc. Natl. Acad. Sci. U. S. A. (2001) 98 4877 4882 10.1073/pnas.051632898 11320237 

  29. 29 Scheerer P. Park J.H. Hildebrand P.W. Kim Y.J. Krauss N. Choe H.W. Hofmann K.P. Ernst O.P. Crystal structure of opsin in its G-protein-interacting conformation. Nature (2008) 455 497 502 10.1038/nature07330 18818650 

  30. 30 Choe H.W. Kim Y.J. Park J.H. Morizumi T. Pai E.F. Krauss N. Hofmann K.P. Scheerer P. Ernst O.P. Crystal structure of metarhodopsin II. Nature (2011) 471 651 655 10.1038/nature09789 21389988 

  31. 31 Taylor J.M. Jacob-Mosier G.G. Lawton R.G. Remmers A.E. Neubig R.R. Binding of an alpha 2 adrenergic receptor third intracellular loop peptide to G beta and the amino terminus of G alpha. J. Biol. Chem. (1994) 269 27618 27624 7961678 

  32. 32 Itoh Y. Cai K. Khorana H.G. Mapping of contact sites in complex formation between light-activated rhodopsin and transducin by covalent crosslinking: use of a chemically preactivated reagent. Proc. Natl. Acad. Sci. U. S. A. (2001) 98 4883 4887 10.1073/pnas.051632998 11320238 

  33. 33 Natochin M. Granovsky A.E. Muradov K.G. Artemyev N.O. Roles of the transducin alpha-subunit alpha4-helixlalpha4-beta6 loop in the receptor and effector interactions. J. Biol. Chem. (1999) 274 7865 7869 10.1074/jbc.274.12.7865 10075679 

  34. 34 Bae H. Cabrera-Vera T.M. Depree K.M. Graber S.G. Hamm H.E. Two amino acids within the alpha4 helix of Galphai1 mediate coupling with 5-hydroxytryptamine1B receptors. J. Biol. Chem. (1999) 274 14963 14971 10.1074/jbc.274.21.14963 10329698 

  35. 35 Johnston C.A. Siderovski D.P. Structural basis for nucleotide exchange on G alpha i subunits and receptor coupling specificity. Proc. Natl. Acad. Sci. U. S. A. (2007) 104 2001 2006 10.1073/pnas.0608599104 17264214 

  36. 36 Grishina G. Berlot C.H. A surface-exposed region of G(salpha) in which substitutions decrease receptor-mediated activation and increase receptor affinity. Mol. Pharmacol. (2000) 57 1081 1092 10825378 

  37. 37 Yu M.Y. Ho M.K. Liu A.M. Wong Y.H. Mutations on the Switch III region and the alpha3 helix of Galpha16 differentially affect receptor coupling and regulation of downstream effectors. J. Mol. Signaling (2008) 3 17 10.1186/1750-2187-3-17 

  38. 38 Westfield G.H. Rasmussen S.G. Su M. Dutta S. DeVree B.T. Chung K.Y. Calinski D. Velez-Ruiz G. Oleskie A.N. Pardon E. Chae P.S. Liu T. Li S. Woods V.L. Jr. Steyaert J. Kobilka B.K. Sunahara R.K. Skiniotis G. Structural flexibility of the G alpha s alpha-helical domain in the beta2-adrenoceptor Gs complex. Proc. Natl. Acad. Sci. U. S. A. (2011) 108 16086 16091 10.1073/pnas.1113645108 21914848 

  39. 39 Abdulaev N.G. Ngo T. Ramon E. Brabazon D.M. Marino J.P. Ridge K.D. The receptor-bound “empty pocket” state of the heterotrimeric G-protein alpha-subunit is conformationally dynamic. Biochemistry (2006) 45 12986 12997 10.1021/bi061088h 17059215 

  40. 40 Van Eps N. Preininger A.M. Alexander N. Kaya A.I. Meier S. Meiler J. Hamm H.E. Hubbell W.L. Interaction of a G protein with an activated receptor opens the interdomain interface in the alpha subunit. Proc. Natl. Acad. Sci. U. S. A. (2011) 108 9420 9424 10.1073/pnas.1105810108 21606326 

  41. 41 Dratz E.A. Furstenau J.E. Lambert C.G. Thireault D.L. Rarick H. Schepers T. Pakhlevaniants S. Hamm H.E. NMR structure of a receptor-bound G-protein peptide. Nature (1993) 363 276 281 10.1038/363276a0 8487866 

  42. 42 Kisselev O.G. Kao J. Ponder J.W. Fann Y.C. Gautam N. Marshall G.R. Light-activated rhodopsin induces structural binding motif in G protein alpha subunit. Proc. Natl. Acad. Sci. U. S. A. (1998) 95 4270 4275 10.1073/pnas.95.8.4270 9539726 

  43. 43 Koenig B.W. Kontaxis G. Mitchell D.C. Louis J.M. Litman B.J. Bax A. Structure and orientation of a G protein fragment in the receptor bound state from residual dipolar couplings. J. Mol. Biol. (2002) 322 441 461 10.1016/S0022-2836(02)00745-3 12217702 

  44. 44 Brabazon D.M. Abdulaev N.G. Marino J.P. Ridge K.D. Evidence for structural changes in carboxyl-terminal peptides of transducin alpha-subunit upon binding a soluble mimic of light-activated rhodopsin. Biochemistry (2003) 42 302 311 10.1021/bi0268899 12525157 

  45. 45 Oldham W.M. Van Eps N. Preininger A.M. Hubbell W.L. Hamm H.E. Mechanism of the receptor-catalyzed activation of heterotrimeric G proteins. Nat. Struct. Mol. Biol. (2006) 13 772 777 10.1038/nsmb1129 16892066 

  46. 46 Orban T. Jastrzebska B. Gupta S. Wang B. Miyagi M. Chance M.R. Palczewski K. Conformational dynamics of activation for the pentameric complex of dimeric G protein-coupled receptor and heterotrimeric G protein. Structure (2012) 20 826 840 10.1016/j.str.2012.03.017 22579250 

  47. 47 Chung K.Y. Rasmussen S.G. Liu T. Li S. DeVree B.T. Chae P.S. Calinski D. Kobilka B.K. Woods V.L. Jr. Sunahara R.K. Conformational changes in the G protein Gs induced by the β2 adrenergic receptor. Nature (2011) 477 611 615 10.1038/nature10488 21956331 

  48. 48 Natochin M. Moussaif M. Artemyev N.O. Probing the mechanism of rhodopsin-catalyzed transducin activation. J. Neurochem. (2001) 77 202 210 10.1046/j.1471-4159.2001.t01-1-00221.x 11279276 

  49. 49 Marin E.P. Krishna A.G. Sakmar T.P. Rapid activation of transducin by mutations distant from the nucleotidebinding site: evidence for a mechanistic model of receptor-catalyzed nucleotide exchange by G proteins. J. Biol. Chem. (2001) 276 27400 27405 10.1074/jbc.C100198200 11356823 

  50. 50 Marin E.P. Krishna A.G. Sakmar T.P. Disruption of the alpha5 helix of transducin impairs rhodopsin-catalyzed nucleotide exchange. Biochemistry (2002) 41 6988 6994 10.1021/bi025514k 12033931 

  51. 51 Kapoor N. Menon S.T. Chauhan R. Sachdev P. Sakmar T.P. Structural evidence for a sequential release mechanism for activation of heterotrimeric G proteins. J. Mol. Biol. (2009) 393 882 897 10.1016/j.jmb.2009.08.043 19703466 

  52. 52 Preininger A.M. Parello J. Meier S.M. Liao G. Hamm H.E. Receptor-mediated changes at the myristoylated amino terminus of Galpha(il) proteins. Biochemistry (2008) 47 10281 10293 10.1021/bi800741r 18771287 

  53. 53 Kisselev O.G. Downs M.A. Rhodopsin controls a conformational switch on the transducin gamma subunit. Structure (2003) 11 367 373 10.1016/S0969-2126(03)00045-5 12679015 

  54. 54 Cherfils J. Chabre M. Activation of G-protein Galpha subunits by receptors through Galpha-Gbeta and Galpha- Ggamma interactions. Trends Biochem. Sci. (2003) 28 13 17 10.1016/S0968-0004(02)00006-3 12517447 

  55. 55 Rondard P. Iiri T. Srinivasan S. Meng E. Fujita T. Bourne H.R. Mutant G protein alpha subunit activated by Gbeta gamma: a model for receptor activation? Proc. Natl. Acad. Sci. U. S. A. (2001) 98 6150 6155 10.1073/pnas.101136198 11344266 

  56. 56 Patowary S. Alvarez-Curto E. Xu T.R. Holz J.D. Oliver J.A. Milligan G. Raicu V. The muscarinic M3 acetylcholine receptor exists as two differently sized complexes at the plasma membrane. Biochem. J. (2013) 452 303 312 10.1042/BJ20121902 23521066 

  57. 57 Watts A.O. van Lipzig M.M. Jaeger W.C. Seeber R.M. van Zwam M. Vinet J. van der Lee M.M. Siderius M. Zaman G.J. Boddeke H.W. Smit M.J. Pfleger K.D. Leurs R. Vischer H.F. Identification and profiling of CXCR3-CXCR4 chemokine receptor heteromer complexes. Br. J. Pharmacol. (2013) 168 1662 1674 10.1111/bph.12064 23170857 

  58. 58 Teitler M. Klein M.T. A new approach for studying GPCR dimers: drug-induced inactivation and reactivation to reveal GPCR dimer function in vitro, in primary culture, and in vivo. Pharmacol. Ther. (2012) 133 205 217 10.1016/j.pharmthera.2011.10.007 22119169 

  59. 59 Ayoub M.A. Al-Senaidy A. Pin J.P. Receptor-G protein interaction studied by bioluminescence resonance energy transfer: lessons from protease-activated receptor 1. Front. Endocrinol. (Lausanne) (2012) 3 82 22737145 

  60. 60 Qin K. Dong C. Wu G. Lambert N.A. Inactivestate preassembly of G(q)-coupled receptors and G(q) heterotrimers. Nat. Chem. Biol. (2011) 7 740 747 10.1038/nchembio.642 21873996 

  61. 61 Qin K. Sethi P.R. Lambert N.A. Abundance and stability of complexes containing inactive G protein-coupled receptors and G proteins. FASEB J. (2008) 22 2920 2927 10.1096/fj.08-105775 18434433 

  62. 62 Gales C. Van Durm J.J. Schaak S. Pontier S. Percherancier Y. Audet M. Paris H. Bouvier M. Probing the activation-promoted structural rearrangements in preassembled receptor-G protein complexes. Nat. Struct. Mol. Biol. (2006) 13 778 786 10.1038/nsmb1134 16906158 

  63. 63 Challiss R.A. Wess J. Receptors: GPCR-G protein preassembly? Nat. Chem. Biol. (2011) 7 657 658 10.1038/nchembio.665 21931312 

저자의 다른 논문 :

LOADING...

관련 콘텐츠

오픈액세스(OA) 유형

GOLD(Hybrid)

저자가 APC(Article Processing Charge)를 지불한 논문에 한하여 자유로운 이용이 가능한, hybrid 저널에 출판된 논문

저작권 관리 안내
섹션별 컨텐츠 바로가기

AI-Helper ※ AI-Helper는 오픈소스 모델을 사용합니다.

AI-Helper 아이콘
AI-Helper
안녕하세요, AI-Helper입니다. 좌측 "선택된 텍스트"에서 텍스트를 선택하여 요약, 번역, 용어설명을 실행하세요.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.

선택된 텍스트

맨위로