GPCR Structures: delta opioid and nociceptin receptors


There will come a point in time when a new GPCR structure doesn't 'make the grade' for Nature or Science, but hopefully that time is still a considerable way off. There are two new GPCR structures released recently - the nociceptin receptor 4ea3 and the delta-opioid receptor 4ej4, bringing it to a grand total of 15 sequence distinct rhodopsin-like GPCR structures in the public domain.

Both new ones published alongside two other previously released PDB entries in last weeks Nature.

Here is an alignment - thanks to the commenter on a previous post in this series that spotted my schoolboy error in a previous version.


  1. 3uon - human muscarinic M2 receptor 
  2. 4daj - rat muscarinic M3 receptor 
  3. 3rze - human histamine H1 receptor
  4. 2rh1 - human beta-2 adrenergic receptor 
  5. 2vt4 - turkey beta-1 adrenergic receptor 
  6. 3pbl - human dopamine D3 receptor
  7. 2ydv - human adenosine A2a receptor 
  8. 3v2w - human sphingosine-1-phosphate receptor 
  9. 4djh - human kappa opioid receptor 
  10. 4dkl - mouse mu opioid receptor 
  11. 4ej4 - mouse delta opioid receptor
  12. 4ea3 - human nociceptin receptor
  13. 3odu - human CCR4 receptor 
  14. 2i35 - bovine rhodopsin 
  15. 2z73 - squid rhodopsin



                           10        20        30        40        50  
3uon   (  20 )                                             tfevvfivl
4dajA  (  64 )                                             iwqvvfiaf
3rze   (  28 )                                                 mplvv
2rh1   (  29 )                                            devwvvgmgi
2vt4A  (  40 )                                               weagmsl
3pblA  (  32 )                                                   yal
2ydv   (   3 )                                             imgssvYit
3v2w   (  17 )           sdyvnydIIvrHYnyTgklnisa                ltsv
4djhA  (  55 )                                            spaipviita
4dkl   (  65 )                                             mvtaitima
4ej4   (  41 )                                        rsasslalaiaita
4ea3A  (  47 )                                            plglkvtIvg
3oduA  (  27 )            pçfre-------------------------enanfnkiflpt
1u19A  (   1 )            mnGtegpnfyVPfsnktgvVrsPFeapQyyLaepwqFsmlAa
2z73A  (   9 )         etwwyNpsIvVhpHWref--------------dqvpdavYyslGi
                                                              aaaaaa

                           60        70        80        90        100 
3uon   (  29 )    vagslSlvTiigNilVmvSIkvnrhLqtvnnyflfSLAcADliiGvfSMn
4dajA  (  73 )    ltgflAlvTiigNilVivAFkvnkqLktvnnyFllSLAcADliIGviSMn
3rze   (  33 )    vlsticlvTvglNllVlyAvrserkLhtvGnlYIvsLSvADliVGavVMp
2rh1   (  39 )    vmslivlaIvfgNvlVitAIakferLqtvtnyFItsLAcADlvMGlaVVp
2vt4A  (  47 )    lmalVvllIvagNvlViaAigstqrLqtltnlFItsLAcADlvvGllVVp
3pblA  (  35 )    sYcalilaIvfgNglVcmAVlkeraLqtttnyLVvsLAvADllvAtlVMp
2ydv   (  12 )    vElaiavlAilgNvlVcwAvwlnsnLqnvtnyFVvsAAaADilVGvlAIp
3v2w   (  51 )    vfiliCcfIileNifvlltiwktkkFhrpMYyFIgnLAlSDllaGvaYta
4djhA  (  65 )    vysvvfvvGlvgNslVmfVIirytkmktaTniYIfNLAlADalVTtTMpf
4dkl   (  74 )    lYsiVcvvGlfgNflvmyvIvrytkMktAtniYIfNLAlADalATsTLpf
4ej4   (  55 )    lYsavcavGllgNvlvmfgIvrytkLktATniYIfNLAlADalATstLpf
4ea3A  (  57 )    lYlavcvgGllgNclvmyVIlrhtkmktatNiYIfNLAlADtlVLlTLpf
3oduA  (  44 )    iYsiIfltGivgNglvilvMgyqkklrsmtdkYRlhLSvADllFVitLpf
1u19A  (  43 )    yMflLimlGfpiNflTlyVTvqHkkLrtplNyILlnLAvADlfMVfg-GF
2z73A  (  40 )    fIgiCgiiGcggNgiViyLFtktksLqtpanmFiinLAfSDftFSlvNGf
                  aaaaaaaaaaaaaaaaaaaaaa      aaaaaaaaaaaaaaaaaa aaa

                           110       120       130       140       150 
3uon   (  79 )    lytlytvi-gyWplgpvvÇdlWlalDYvVSNAsVmNLliiSfdryfcvtk
4dajA  ( 123 )    lFttyiim-nrWalgnlaÇdlwLSiDYvASNAsVmNLlvISfDryfsitr
3rze   (  83 )    mnilyllm-skwsLgrplÇlfWLSmDYVASTASIfSVfiLCiDryrsvqq
2rh1   (  89 )    fgaahilm-kmWtfgnfwçefWTSiDVlCVTASIeTLcvIAvdryfAIts
2vt4A  (  97 )    fgatlvvr-gtWlwgsflçelWTSlDVlCVTAsIeTLcvIAiDrylaits
3pblA  (  85 )    wvvylevtggvWnfsricÇdvFVTlDVmMcTAsIwNLCaISidRytAVvm
2ydv   (  62 )    faiaIst---GfçaaçhgÇLfiACfVLVLTASSIfSLlaIAiDryiairi
3v2w   ( 101 )    Nlllsga--tTykLtPaqWFlREGsMFvALSASVfSLlaIAieryitmlk
4djhA  ( 115 )    qstvylmn--sWpfgdvlÇkiVlsiDyyNMfTSIfTLtmMSvdRyiaVch
4dkl   ( 124 )    qsvnylmg--tWpfgnilÇkiviSidYyNMFTSIfTLctMSvdRyiAVCh
4ej4   ( 105 )    qsakylme--tWpfgellÇkaVlSidYyNMFTSIfTLtmMSvDRyiavch
4ea3A  ( 107 )    QGtdillg--fWpfgnalÇktVIaiDyyNMFTSTfTLtaMSvdryvaich
3oduA  (  94 )    WavDAva---nWyfgnflÇkaVHviYTVNlYSSVwILAfISlDRylAiVh
1u19A  (  92 )    tTTlyTSlhGyFvfgptGÇnlEGffATLGGEIaLWSLvvLaieRyvvVck
2z73A  (  90 )    plMtiSCflkkWifgfaaÇkvYGfiGGiFGFMsIMTMAMiSiDrynViGr
                  aaaaaaa        aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa  

                           160       170       180       190       200 
3uon   ( 128 )    pltypvk---rttkmAgmmiaaAwvlSfilwapaIlfwqfivg-------
4dajA  ( 172 )    pltyrak---rttkrAgvmiglAwviSfvlWApaIlfwqyfvg-------
3rze   ( 132 )    plrylky---rtktrAsatilgawflSfl-WvipIlgwnh          
2rh1   ( 138 )    pfkyqSl---ltknkArviilmvwivSgltSflpIqmhwyr-----athq
2vt4A  ( 146 )    pfryqsl---mtrarAkviictvwaiSalvSflpImmhwWr-----dedp
3pblA  ( 135 )    pvhyqhgtgqsscrrValmitavwvlAfaVSc-pLlfgfNtTg-------
2ydv   ( 109 )    plryngl---vtgtrAkgiiaicwvlSfaIGltPmlgwnnÇgqp--kegk
3v2w   ( 156 )               nnfrlfllisacwviSlilGglPimgwn-----------
4djhA  ( 163 )    pvkaldf---rtplkAkiinicIwllSssvGisAivlGGtkvred-----
4dkl   ( 172 )    pvkaldf---rtprnAkivnvcNwilSsaiGlpVmfmAttkyrqg-----
4ej4   ( 153 )    pvkaldf---rtpakAklinicIwvlAsgvGvpimvmAvtqprdg-----
4ea3A  ( 155 )    p          tsskAqavnvaIwalAsvvGvpvaimGsAqvede-----
3oduA  ( 141 )    atn---sqrprkllAekvVyvgVwipAlllT-ipDfif--Anvsead---
1u19A  ( 142 )    pmsn----frfgenhaimgvafTwvmAlaCAapPlvgwSrYIPE------
2z73A  ( 140 )    pmaas---kkMshrrAfimiifVwlwSvlwAigPifgwGaYtLE------
                              aaaaaaaaaaaaaaaaaaaa aaa              

                           210       220       230       240       250 
3uon   ( 168 )    ----vrtVedgeÇyIqff------snaavtfgtAiaaFylpviiMtvlyw
4dajA  ( 212 )    ----krtVppgeÇfIqfl------septitfgtAiaaFymPvtiMtilyw
3rze   ( 175 )           rredkÇeTdfy------dvtwfkvmtaiinFylPtllMlwfya
2rh1   ( 180 )    eAinÇyae-etçÇdff--------TnqayaiasSivSFyvplviMvfvYs
2vt4A  ( 188 )    qAlkçyqd-pgçÇdfv--------TnrayaiasSiiSFyipLliMifval
3pblA  ( 177 )    --------dptvÇsIs---------npdFViySSvvSFylPfgvTvlvya
2ydv   ( 154 )    ahsqgÇgegqvAÇlFedVV-----pmnYMVyfNffaCVlvPlllMlgvyl
3v2w   ( 184 )    ----ÇisalssÇSTVLP-------LYhkhYIlfCTtvFtllllsIvilYc
4djhA  ( 205 )    -------vdvieÇslqFpdddyswwdlfmkicVfifAfviPvliIivcyt
4dkl   ( 214 )    ---------sidçtltfsh-ptwywenllKicVfifAfimPvliItvcyg
4ej4   ( 195 )    ---------avvÇmlqfps-pswywdtvtkicvflfAfvvPiliitvcyg
4ea3A  ( 197 )    ---------eieÇlveipt-pqdywgpvfaiciflfSFivPvlvIsvcys
3oduA  ( 182 )    --------dryiÇdrfyp---ndlwvvvfqfqhimvglilPgivIlsCyc
1u19A  ( 182 )    -------GMQCSÇGIDYYTpheetnNesFViyMfvvHfiiPlivIffcyg
2z73A  ( 181 )    -------GVLCNÇSFdYIsr--dsttrsNIlcMFilGffgPiliiffCyf
                                            aaaaaaaaaa  aaaaaaaaaaaa

                           260       270       280       290       300 
3uon   ( 208 )    hisrasksri                   pppsrekkvtrtilaIllaFi
4dajA  ( 252 )    rIyketek                       like   aqTlsaIllaFi
3rze   ( 212 )    kIykaVrqhc                   lhmnrerkaakQLgfIMaaFi
2rh1   ( 221 )    rVfqeakrql                   kfclkeHkaLktlgiIMgtFt
2vt4A  ( 229 )    rvyreakeq                       irehkalktlgiImgvFt
3pblA  ( 210 )    rIyvvlkqrrrk-----------------gvplrekkatqMVaiVlgaFi
2ydv   ( 199 )    rIflaarrqlkqmesq             stlqkevhaakSLaiIvglFa
3v2w   ( 223 )    riyslvrtr                   asrssenvaLlkTViiVLsvFi
4djhA  ( 248 )    lMilrlksvrllsg              rekdrnlrritrLVlvVVavFv
4dkl   ( 254 )    lmilrlksvr                   ekdrnlrritrMVlvVvavFi
4ej4   ( 235 )    lMllrlrsvr                   ekdrslrriTrMVlvVvgaFv
4ea3A  ( 237 )    lMirrlrgvrlls-------------gsrekdrnlrritrLVlvVvavFv
3oduA  ( 221 )    iIisklshs                     kghqkrkalktTviLilaFf
1u19A  ( 225 )    qLvftvkeaaaq------------qqesattqkaekevTrMviiMviaFl
2z73A  ( 222 )    nIvmsvsnhekemaamakrlnakelrkaqaganaemrlAkIsivIVsqFl
                  aaaaa                            aaaaaaaaaaaaaaaaa

                           310       320       330       340       350 
3uon   ( 398 )    itWapYNvmVlintfçap--------ç--ipntvwtiGywlCYinstiNp
4dajA  ( 501 )    itWtpyNimVlvntfçds--------ç--ipktywnlgywlCYiNStvNP
3rze   ( 426 )    lCWipYFiffmviafçkn--------ç--cnehlhmftiWlGYiNStlNP
2rh1   ( 284 )    lcWlpFFiVNivhviqdn----------lirkevyillNwiGYvNSgfNp
2vt4A  ( 301 )    lCWlpFFlvnivnvfnrd----------lvpdwlfvafnwlGYAnSAmnp
3pblA  ( 340 )    vCWlpFFltHvlnthçqt--------ç-hvspelysattwlGYvNsalNP
2ydv   ( 244 )    lCWlpLHiiNcftffçpd--------çshaplwlMylAivlSHtNSvvNP
3v2w   ( 267 )    acwapLFiLLllDvgçkvk------tç--diLfrAeyfLvlAvlNSgtNP
4djhA  ( 285 )    vcWtpIHifilvealgs            aalssyyfcIalGytNSslNP
4dkl   ( 291 )    vcWtpIHiyViikaliti-------pettfqtvswhfcialGYtNSclNp
4ej4   ( 272 )    vCWapIHifVivwtlvdi------nrrdplvvaalhlcialGYaNSslNp
4ea3A  ( 274 )    gcWtpVQvfvlaqglgvq-------pssetavailrfctAlGYvNSclNp
3oduA  ( 250 )    acWlpyyigisidsfilleiikqgçefentvhkwisitEAlAFfHCclNp
1u19A  ( 263 )    iCWlpYAgvAfyIfthqgsd---------fgpifMTipAFfAKtSAvyNP
2z73A  ( 272 )    lSWspYAvvAllAQfgplew---------VtpyaAQlpVMfAKaSaihNP
                  aaaaaaaaaaaaaaa                aaaaaaaaaaaaa   aaa

                           360       370       380       390       400 
3uon   ( 438 )    acYalcnatFkktfkhllm                               
4dajA  ( 541 )    vcYalcnktFrttfkt                                  
3rze   ( 466 )    liYplCnenFkktfkrilhi                              
2rh1   ( 324 )    liYc-rspdfriAfqellcl                              
2vt4A  ( 341 )    iiYc-rspdfrkAfkrlla                               
3pblA  ( 381 )    viYttfnieFrkAflkilsc                              
2ydv   ( 286 )    fiyAyrireFrqTFrkiirshvlrqqepfkaa                  
3v2w   ( 309 )    iiytltNkemrrafiri                                 
4djhA  ( 328 )    ilYafldenFkrcfrdfcfp                              
4dkl   ( 334 )    vlYafldenFkrCfrefci                               
4ej4   ( 316 )    vlYaflDenfkrc                                     
4ea3A  ( 317 )    ilYafldenFkacfr                                   
3oduA  ( 300 )    ilyaflgakfktsaqhalts                              
1u19A  ( 304 )    viYimmnkqFrnCmvttlccgknplgddeasttVsktetsqvapa     
2z73A  ( 313 )    miYsvsHpkFreAIsqtfpwvLtccqfddketeddkdaeteipage    
                  aaaaa  aaaaaaaaaa                                 

                           410

%T Crystal structure of the µ-opioid receptor bound to a morphinan antagonist
%A A. Manglik
%A A.C. Kruse
%A T.S. Kobilka
%A F.S. Thian
%A J.M. Mathiesen
%A R.K. Sunahara
%A L. Pardo
%A W.I. Weis
%A B.K. Kobilka
%A S. Granier
%J Nature 
%V 485
%P 321–326
%O doi:10.1038/nature10954
%D 2012

%T Structure of the human κ-opioid receptor in complex with JDTic
%A H. Wu
%A D. Wacker
%A M. Mileni
%A V. Katritch
%A G.W. Han
%A E. Vardy
%A W. Liu
%A A.A. Thompson
%A X.-P. Huang
%A F.I. Carroll
%A S.W. Mascarella
%A R.B. Westkaemper
%A P.D. Mosier
%A B.L. Roth
%A V. Cherezov
%A R.C. Stevens
%J Nature 
%V 485
%P 327–332
%O doi:10.1038/nature10939
%D 2012

%T Structure of the nociceptin/orphanin FQ receptor in complex with a peptide mimetic
%A A.A. Thompson
%A W. Liu,  
%A E. Chun
%A V. Katritch
%A H. Wu
%A E. Vardy
%A X.-P. Huang
%A C. Trapella
%A R. Guerrini
%A G. Calo
%A B.L. Roth
%A V. Cherezov
%A R.C. Stevens
%J Nature 
%V 485
%P 395–399
%O doi:10.1038/nature11085
%D 2012

%T Structure of the δ-opioid receptor bound to naltrindole
%A S. Granier
%A A. Manglik
%A A.C. Kruse
%A T.S. Kobilka
%A F.S. Thian
%A W.I. Weis 
%A B.K. Kobilka
%J Nature
%V 485
%P 400–404
%O doi:10.1038/nature11111
%D 2012