Table 1.
Comparison of the distance between the TM helices III and VI in X-ray crystal and cryo-EM structures of GPCR complexes with agonists and antagonists
| GPCR | PDB ID | Ligand* | TM III3.32† | TM VI6.51† | d (Å)‡ | Δd (Å)§ | Bound protein¶ |
|---|---|---|---|---|---|---|---|
| A1R | 6D9H | Adenosine | V87 | L250 | 14.1 | 1.2 | Gi |
| 5UEN | DU172 | 12.9 | — | ||||
| A2AAR | 6GDG | NECA | V84 | L249 | 14.5 | 1.4 | Nb35 |
| 4EIY | ZM241385 | 13.1 | — | ||||
| AT1R | 6DO1 | S1I8 | V108 | H256 | 13.3 | −0.6 | NbAT110i1 |
| 4YAY | ZD7155 | 13.9 | — | ||||
| AT2R | 5XJM | S1I8 | L124 | F272 | 15.3 | −0.3 | Fab |
| 5UNG | 8ES | 15.6 | — | ||||
| β1AR | 6H7J | Isoprenaline | D138 | F340 | 13.8 | 0.4 | Nb80 |
| 2VT4 | (S)-Cyanopindolol | 13.4 | — | ||||
| β2AR | 3SN6 | Bl-167107 | D113 | F289 | 14.2 | 0.5 | Gs |
| 2RH1 | Carazolol | 13.7 | — | ||||
| CB1 | 6N4B | MDMB-FUB | V196 | L359 | 14.4 | 1.9 | Gi |
| 5TGZ | AM6538 | 12.5 | — | ||||
| CB2 | 6KPF | AM841 | V113 | V261 | 14.0 | −0.7 | Gi |
| 5ZTY | AM10257 | 14.7 | — | ||||
| CCR5 | 7F1R | CCL5 | Y108 | Y251 | 15.4 | 0.3 | Gi |
| 4MBS | Maraviroc | 15.1 | — | ||||
| D2R | 6VMS | Bromocriptine | D114 | F389 | 14.4 | 0.5 | Gi |
| 6LUQ | Haloperidol | 13.9 | — | ||||
| D3R | 7CMU | Pramipexole | D110 | F345 | 14.1 | 0.2 | Gi |
| 3PBL | Eticlopride | 13.9 | — | ||||
| δOR | 6PT2 | KGCHM07 | D128 | I277 | 14.5 | 1.2 | — |
| 4N6H | Naltrindole | 13.3 | — | ||||
| ETBR | 5GLH | Endothelin-1 | Q181 | L339 | 13.8 | −1.0 | — |
| 5X93 | K-8794 | 14.8 | — | ||||
| EP4R | 7D7M | Prostaglandin E2 | L99 | L288 | 12.6 | 2.2 | Gs |
| 5YWY | ONO-AE3-208 | 10.4 | — | ||||
| FFAR1 | 4PHU | TAK-875 | H86 | Y240 | 12.9 | −0.4 | — |
| 5KW2 | Propanoic acid | 13.3 | — | ||||
| H1R | 7DFL | Histamine | D107 | Y431 | 13.5 | −0.7 | Gq |
| 3RZE | Doxepin | 14.2 | — | ||||
| κOR | 6B73 | MP1104 | D138 | I290 | 14.1 | 1.4 | Nb39 |
| 4DJH | JDTic | 12.7 | — | ||||
| M2R | 4MQS | Iperoxo | D103 | Y403 | 14.0 | −0.6 | Nb9-8 |
| 3UON | (R)-QNB | 14.6 | — | ||||
| MC4R | 7AUE | Aminoserine | I129 | F261 | 13.7 | 0.6 | Gs |
| 6W25 | SHU9119 | 13.1 | — | ||||
| MT1AR | 7DB6 | Ramelteon | M107 | L254 | 15.2 | 1.1 | Gi |
| 6PS8 | 2-phenylmelatonin | 14.1 | — | ||||
| μOR | 6DDF | DAMGO | D149 | I296 | 14.1 | 0.7 | Gi |
| 4DKL | BF0 | 13.4 | — | ||||
| NK1R | 7RMH | SP | P112 | F264 | 15.6 | 2.9 | Gs |
| 6J20 | aprepitant | 12.7 | — | ||||
| OX2R | 7L1U | Orexin-A | Q134 | I320 | 13.7 | 0.8 | Gs |
| 5WQC | EMPA | 12.9 | — | ||||
| P2Y12R | 4PXZ | 2-MeSADP | F104 | F252 | 11.8 | −0.3 | — |
| 4NTJ | AZD1283 | 12.1 | — | ||||
| 5-HT1BR | 6G79 | Donitriptan | D129 | F330 | 13.2 | −0.9 | Go |
| 5V54 | Methiothepin | 14.1 | — | ||||
| 5-HT2AR | 6WHA | 25-CN-NBOH | D155 | F339 | 15.0 | 1.1 | Gq |
| 6A94 | Zotepine | 13.9 | — | ||||
| 5-HT2BR | 5TUD | Ergotamine | D135 | F340 | 13.4 | −0.5 | — |
| 6DRZ | Methysergide | 13.9 | — | ||||
| 5-HT2CR | 6BQG | Ergotamine | D134 | F330 | 13.6 | −0.7 | — |
| 6BQH | Ritanserin | 14.3 | — |
*Orthosteric ligand bound; for each receptor the agonist is listed first.
†Ballesteros–Weinstein notation of the residues in TM III and TM VI between which the Cα–Cα distance was evaluated.
‡Distance between the α-carbons of residues 3.32 and 6.51.
§Difference between the two structures of each receptor; negative numbers represent that the distance in the agonist-bound structure is smaller than in the antagonist-bound structure.
¶Intracellular partner protein bound in a tertiary complex with GPCR and an orthosteric ligand; the structures of all but one of the tertiary complexes resulted from cryo-EM studies.