GPCRs of Known Structure
So far eight different types of GPCR structures have been determined by X-ray crystallography: β2 Adrenergic Receptor, β1 Adrenergic Receptor, Adenosine Receptor, Rhodopsin, CXCR4 Chemokine receptor, Dopamine D3 receptor, the Histamine Receptor and the S1P1 Sphingosine 1-phosphate receptor.
Updates:
- 7 Oct 2010: added CXCR4 Chemokine Receptor
- 18 Nov 2010: added Dopamine D3 Receptor
- The tables below makes it easier to find them either as a PDB code or the original reference.
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21 Jan 2011: β1 and β2 Adrenergic Receptor structures
stabilized active state of β2 Adrenergic Receptor: 3P0G with irreversible agonist: 3PDS partial agonist and agonist structures of β1 2y00, 2Y01, 2Y02, 2Y03, 2Y04 - 27 March 2011: A2A Adenonsine Receptor with bound agonist: 3QAK
- 30 March 2011: Dobutamin bound beta 1 adrenergic receptor (turkey): 2Y01
- 22 June 2011: Histamine H1 Recepotor bound to doxepin: 3RZE ; A2A Adenosine Receptor with bound agonists Adenosine 2YDO & NECA 2YDV
- 20 July 2011: agonist-occupied β2 adrenergic receptor (active) in complex with the (nucleotide free) Gs heterotrimer: 3SN6
- 17 Feb 2012: sphingosine 1-phosphate receptor 1 (S1P1-T4L) with a bound sphingolipid mimic (antagonist): 3v2W
If there's a new GPCR structure out there and it's not on this list: drop me a line so I can included it here.
Thanks!
Peter
Histamine H1 Receptor
| Structure Notes | PDB | Resolution [A] | Reference |
|---|---|---|---|
| H1R with bound drug molecule doxepin | 3RZE | 3.1 | T.Shimamura, M. Shiroishi, S. Weyand, H.Tsujimoto, G. Winter, V. Katritch, R. Abagyan, V. Cherezov, W. Liu, G.W. Han, T. Kobayashi, R.C. Stevens & So Iwata Structure of the human histamine H1 receptor complex with doxepin Nature (2011) doi:10.1038/nature10236 |
Sphingosine 1-phosphate Receptor
| Structure Notes | PDB | Resolution [A] | Reference |
|---|---|---|---|
| sphingosine 1-phosphate receptor 1 (S1P1-T4L) with a bound sphingolipid mimic (antagonist) | 3V2W | 3.35 | Crystal Structure of a Lipid G Protein–Coupled Receptor Michael A. Hanson, Christopher B. Roth, Euijung Jo,Mark T. Griffith, Fiona L. Scott, Greg Reinhart, Hans Desale, Bryan Clemons, Stuart M. Cahalan, Stephan C. Schuerer, M. Germana Sanna, Gye Won Han, Peter Kuhn, Hugh Rosen, Raymond C. Stevens Science Vol. 335 no. 6070 pp. 851-855; 2012 |
Dopamine D3 Receptor
| Structure Notes | PDB | Resolution [A] | Reference |
|---|---|---|---|
| D(3) dopamine receptor, T4 lysozyme insertion in 3rd intracellular loop, in complex with Eticlopride, crystallized in LCP (Cholesterol additive) | 3PBL | 2.9 A | No publication yet. PDB authors: Chien, E.Y.T., Liu, W., Han, G.W., Katritch, V., Zhao, Q., Cherezov, V., Stevens, R.C., Accelerated Technologies Center for Gene to 3D Structure (ATCG3D) |
Rhodopsin
| Structure Notes | PDB | Resolution [A] | Reference |
|---|---|---|---|
| first experimental GPCR structures | 1F88, 1HZX | 2.8 | Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Miyano M. Science. 2000 Aug Crystal structure of rhodopsin: A G protein-coupled receptor. 4;289(5480):739-45. Teller DC, Okada T, Behnke CA, Palczewski K, Stenkamp RE. Advances in determination of a high-resolution three-dimensional structure of rhodopsin, a model of G-protein-coupled receptors (GPCRs). Biochemistry. 2001 Jul 3;40(26):7761-72. |
| shows functional water molecules | 1L9H | 2.6 | Okada T, Fujiyoshi Y, Silow M, Navarro J, Landau EM, Shichida Y. Functional role of internal water molecules in rhodopsin revealed by X-ray crystallography. Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):5982-7. Epub 2002 Apr 23. |
| focus on retinal conformation | 1U19 | 2.2 | Okada T, Sugihara M, Bondar AN, Elstner M, Entel P, Buss V. The retinal conformation and its environment in rhodopsin in light of a new 2.2 A crystal structure. J Mol Biol. 2004 Sep 10;342(2):571-83. |
| Thermostable N2C/D282C mutant heterologously expressed in COS cells | 2J4Y | 3.4 | Standfuss J, Xie G, Edwards PC, Burghammer M, Oprian DD, Schertler GF. Crystal structure of a thermally stable rhodopsin mutant. J Mol Biol. 2007 Oct 5;372(5):1179-88. Epub 2007 Mar 12. |
| photoactivated and ground state | 2I35, 2I36, 2I37 | 3.8, 4.1, 4.15 | Salom D, Lodowski DT, Stenkamp RE, Le Trong I, Golczak M, Jastrzebska B, Harris T, Ballesteros JA, Palczewski K. Crystal structure of a photoactivated deprotonated intermediate of rhodopsin. Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16123-8. Epub 2006 Oct 23 |
| Retinal removed: Opsin | 3CAP | 2.9 | Park JH, Scheerer P, Hofmann KP, Choe HW, Ernst OP. Nature. 2008 Jul 10;454(7201):183-7. Epub 2008 Jun 18. Crystal structure of the ligand-free G-protein-coupled receptor opsin. |
| activated form of Ops*-GalphaCT peptide complex | 3DQB | 3.2 | Scheerer P, Park JH, Hildebrand PW, Kim YJ, Krauss N, Choe HW, Hofmann KP, Ernst OP. Crystal structure of opsin in its G-protein-interacting conformation. Nature. 2008 Sep 25;455(7212):497-502. |
| Squid Rhodopsin | 2Z73 | 2.5 | Murakami M, Kouyama T. Crystal structure of squid rhodopsin. Nature. 2008 May 15;453(7193):363-7. |
CXCR4 Chemokine Receptor
| Structure Notes | PDB | Resolution [A] | Reference |
|---|---|---|---|
| complex with small molecule antagonist IT1t and cyclic peptide antagonist CVX15, T4 lysozyme insertion in 3rd intracellular loop, stabilizing mutations, crystallized in LCP (Cholesterol additive) | 3ODU, 3OE0, 3OE8, 3OE9, 3OE6 | 2.5 A, 2.9 A, 3.1 A, 3.1 A, 3.2 A | Wu, B. et al., Structures of the CXCR4 Chemokine GPCR with Small-Molecule and Cyclic Peptide Antagonists. Science 7 Oct 2010 |
β1 Adrenergic Receptor
| Structure Notes | PDB | Resolution [A] | Reference |
|---|---|---|---|
| Dobutamin bound beta 1 adrenergic receptor (turkey) | 2Y01 | 2.6 | Warne, A. et al. (2011) TURKEY BETA1 ADRENERGIC RECEPTOR WITH STABILISING MUTATIONS AND BOUND PARTIAL AGONIST DOBUTAMINE (CRYSTAL DOB102) Nature 469: 241 |
| Thermostabilized turkey receptor | 2VT4 | 2.7 | Warne T. et al., (2008) Structure of a beta1-adrenergic G-protein-coupled receptor Nature 454, 486-491 |
Adenosine Receptor
| Structure Notes | PDB | Resolution [A] | Reference |
|---|---|---|---|
| Bound antagonist ZM241385 | 3EML | 2.6 | Jaakola VP, Griffith MT, Hanson MA, Cherezov V, Chien EY, Lane JR, Ijzerman AP, Stevens RC. The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist. Science. 2008 Nov 21;322(5905):1211-7. Epub 2008 Oct 2. |
| Bound agonist UK-432097 | 3QAK | 2.7 | Structure of an Agonist-Bound Human A2A Adenosine Receptor Xu, F., Wu, H., Katritch, V., Han, G.W., Jacobson, K.A., Gao, Z-D., Cherezov, V., Stevens, R.C. Science DOI: 10.1126/science.1202793 |
| Bound to agonists adenosine and NECA | 2YDO 2YDV | 3.0 & 2.6 | G. Lebon, T. Warne, P. C. Edwards, K. Bennett, C. J. Langmead, A. G. W. Leslie & C. G. Tate Agonist-bound adenosine A(2A) receptor structures reveal common features of GPCR activation Nature 474, 521–525 (23 June 2011) |
| A2A adrenergic receptor bound to Fab2839 | 3VG9 3VGA |
3.1 & 2.7 | Hino, T., Arakawa, T., Iwanari, H., Yurugi-Kobayashi, T., Ikeda-Suno, C., Nakada-Nakura, Y., Kusano-Arai, O., Weyand, S., Shimamura, T., Nomura, N., Cameron, A., Kobayashi, T., Hamakubo, T., Iwata, S., & Murata, T. (2012). G-protein-coupled receptor inactivation by an allosteric inverse-agonist antibody |
β2 Adrenergic Receptor
| Structure Notes | PDB | Resolution [A] | Reference |
|---|---|---|---|
| b2AR365-Fab5 complex | 2R4S, 2R4R | 3.4 / 3.4 | Rasmussen SG, Choi HJ, Rosenbaum DM, Kobilka TS, Thian FS, Edwards PC, Burghammer M, Ratnala VR, Sanishvili R, Fischetti RF, Schertler GF, Weis WI, & Kobilka BK (2007). Crystal structure of the human β2 adrenergic G-protein-coupled receptor. Nature 450:383-387. |
| Complex with Carazolol ligand and bound Cholesterol; T4 lysozyme fusion in 3rd intracellular loop | 2RH1 | 2.4 | Cherezov et al. (2007). High-resolution crystal structure of an engineered human β2-adrenergic G protein-coupled receptor. Science 318:1258-1265 |
| T4 lysozyme fusion in 3rd intracellular loop, bound cholesterol | 3D4S | 2.8 | Hanson et al., (2008) A specific cholesterol binding site is established by the 2.8 A structure of the human beta2-adrenergic receptor. Structure 16: 897-905 |
| methylated receptor | 3KJ6 | 3.4 | Bokoch et al., (2010) Ligand-specific regulation of the extracellular surface of a G-protein-coupled receptor. (2010) Nature 463: 108-112 |
| T4 lysozyme fusion in 3rd intracellular loop, bound cholesterol, mutations: E122W, N187E, C1054T, C1097A; inverse agonist ICI 118,551 | 3NY8 | 2.84 | To be Published: Crystal structure of the human beta2 adrenergic receptor in complex with the inverse agonist ICI 118,551 |
| T4 lysozyme fusion in 3rd intracellular loop, bound cholesterol, mutations: E122W, N187E, C1054T, C1097A; Timolol | 3NY9 | 2.48 | To be published: Crystal structure of the human beta2 adrenergic receptor in complex with a novel inverse agonist |
| T4 lysozyme fusion in 3rd intracellular loop, bound cholesterol, mutations: E122W, N187E, C1054T, C1097A; antagonist alprenolol | 3NYA | 3.16 | Conserved binding mode of human beta2 adrenergic receptor inverse agonists and antagonist revealed by X-ray crystallography |
| agonist-occupied β2 adrenergic receptor (active) in complex with the (nucleotide free) Gs heterotrimer | 3SN6 | 3.2 | Rasmussen et al. Crystal structure of the β2 adrenergic receptor–Gs protein complex Nature (2011) |