4IAQ

Crystal structure of the chimeric protein of 5-HT1B-BRIL in complex with dihydroergotamine (PSI Community Target)

Summary for 4IAQ

• Entry DOI: 10.2210/pdb4iaq/pdb
• Related: 4IAR
• Descriptor: Chimera protein of human 5-hydroxytryptamine receptor 1B and E. Coli soluble cytochrome b562, Dihydroergotamine (3 entities in total)
• Functional Keywords: dihydroergotamine, novel protein engineering, gpcr network, membrane protein, psi-biology, structural genomics, gpcr, signaling protein, electron transport, gpcr dock
• Biological source: Homo sapiens; More
• Cellular location: Cell membrane ; Multi-pass membrane protein : P28222
• Total number of polymer chains: 1
• Total formula weight: 46100.71

Authors

Wang, C.,Jiang, Y.,Ma, J.,Wu, H.,Wacker, D.,Katritch, V.,Han, G.W.,Liu, W.,Huang, X.,Vardy, E.,McCorvy, J.D.,Gao, X.,Zhou, E.X.,Melcher, K.,Zhang, C.,Bai, F.,Yang, H.,Yang, L.,Jiang, H.,Roth, B.L.,Cherezov, V.,Stevens, R.C.,Xu, H.E.,GPCR Network (GPCR) (deposition date: 2012-12-07, release date: 2013-03-13, Last modification date: 2024-11-06)

Primary citation

Wang, C.,Jiang, Y.,Ma, J.,Wu, H.,Wacker, D.,Katritch, V.,Han, G.W.,Liu, W.,Huang, X.P.,Vardy, E.,McCorvy, J.D.,Gao, X.,Zhou, X.E.,Melcher, K.,Zhang, C.,Bai, F.,Yang, H.,Yang, L.,Jiang, H.,Roth, B.L.,Cherezov, V.,Stevens, R.C.,Xu, H.E.
Structural basis for molecular recognition at serotonin receptors.
Science, 340:610-614, 2013

PubMed Abstract: Serotonin or 5-hydroxytryptamine (5-HT) regulates a wide spectrum of human physiology through the 5-HT receptor family. We report the crystal structures of the human 5-HT1B G protein-coupled receptor bound to the agonist antimigraine medications ergotamine and dihydroergotamine. The structures reveal similar binding modes for these ligands, which occupy the orthosteric pocket and an extended binding pocket close to the extracellular loops. The orthosteric pocket is formed by residues conserved in the 5-HT receptor family, clarifying the family-wide agonist activity of 5-HT. Compared with the structure of the 5-HT2B receptor, the 5-HT1B receptor displays a 3 angstrom outward shift at the extracellular end of helix V, resulting in a more open extended pocket that explains subtype selectivity. Together with docking and mutagenesis studies, these structures provide a comprehensive structural basis for understanding receptor-ligand interactions and designing subtype-selective serotonergic drugs.

PubMed: 23519210
DOI: 10.1126/science.1232807

Experimental method

X-RAY DIFFRACTION (2.8 Å)