4IB4

Crystal structure of the chimeric protein of 5-HT2B-BRIL in complex with ergotamine

Summary for 4IB4

• Entry DOI: 10.2210/pdb4ib4/pdb
• Descriptor: Chimera protein of human 5-hydroxytryptamine receptor 2B and E. Coli soluble cytochrome b562, Ergotamine, PALMITIC ACID, ... (9 entities in total)
• Functional Keywords: ergotamine, novel protein engineering, gpcr network, membrane protein, psi-biology, structural genomics, gpcr, signaling protein, electron transport, gpcr dock
• Biological source: Homo sapiens (Human); More
• Cellular location: Cell membrane ; Multi- pass membrane protein : P41595
• Total number of polymer chains: 1
• Total formula weight: 51711.33

Authors

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

Primary citation

Wacker, D.,Wang, C.,Katritch, V.,Han, G.W.,Huang, X.P.,Vardy, E.,McCorvy, J.D.,Jiang, Y.,Chu, M.,Siu, F.Y.,Liu, W.,Xu, H.E.,Cherezov, V.,Roth, B.L.,Stevens, R.C.
Structural features for functional selectivity at serotonin receptors.
Science, 340:615-619, 2013

PubMed Abstract: Drugs active at G protein-coupled receptors (GPCRs) can differentially modulate either canonical or noncanonical signaling pathways via a phenomenon known as functional selectivity or biased signaling. We report biochemical studies showing that the hallucinogen lysergic acid diethylamide, its precursor ergotamine (ERG), and related ergolines display strong functional selectivity for β-arrestin signaling at the 5-HT2B 5-hydroxytryptamine (5-HT) receptor, whereas they are relatively unbiased at the 5-HT1B receptor. To investigate the structural basis for biased signaling, we determined the crystal structure of the human 5-HT2B receptor bound to ERG and compared it with the 5-HT1B/ERG structure. Given the relatively poor understanding of GPCR structure and function to date, insight into different GPCR signaling pathways is important to better understand both adverse and favorable therapeutic activities.

PubMed: 23519215
DOI: 10.1126/science.1232808

Experimental method

X-RAY DIFFRACTION (2.7 Å)