PDB-6p9x: CRF1 Receptor Gs GPCR protein complex with CRF1 peptide

Basic information

• Entry: Database: PDB / ID: 6p9x
• Title: CRF1 Receptor Gs GPCR protein complex with CRF1 peptide

Components

• (Guanine nucleotide-binding protein ...) x 3
• Corticoliberin
• Corticotropin-releasing factor receptor 1
• Nanobody 35

• Keywords: MEMBRANE PROTEIN / GPCR

Function / homology

Function:

corticotropin-releasing hormone activity / positive regulation of digestive system process / positive regulation of corticosterone secretion / regulation of adenylate cyclase activity involved in G protein-coupled receptor signaling pathway / corticotropin-releasing hormone binding / positive regulation of circadian sleep/wake cycle, wakefulness / negative regulation of circadian sleep/wake cycle, REM sleep / regulation of corticosterone secretion / corticotrophin-releasing factor receptor activity / corticotropin-releasing hormone receptor activity / corticotropin-releasing hormone receptor 2 binding / corticotropin secretion / positive regulation of corticotropin secretion / positive regulation of cortisol secretion / regulation of serotonin secretion / general adaptation syndrome, behavioral process / negative regulation of glucagon secretion / MECP2 regulates transcription of neuronal ligands / positive regulation of behavioral fear response / glucocorticoid biosynthetic process / negative regulation of norepinephrine secretion / parturition / hormone-mediated apoptotic signaling pathway / negative regulation of luteinizing hormone secretion / negative regulation of epinephrine secretion / monoatomic ion homeostasis / cellular response to corticotropin-releasing hormone stimulus / negative regulation of voltage-gated calcium channel activity / varicosity / behavioral response to ethanol / positive regulation of cAMP-mediated signaling / response to ether / fear response / neuropeptide hormone activity / synaptic transmission, dopaminergic / G protein-coupled peptide receptor activity / negative regulation of systemic arterial blood pressure / Class B/2 (Secretin family receptors) / regulation of NMDA receptor activity / cellular response to cocaine / diterpenoid metabolic process / exploration behavior / adrenal gland development / hypothalamus development / response to pain / response to aldosterone / response to corticosterone / positive regulation of calcium ion import / locomotory exploration behavior / positive regulation of insulin secretion involved in cellular response to glucose stimulus / associative learning / PKA activation in glucagon signalling / hair follicle placode formation / response to immobilization stress / mu-type opioid receptor binding / developmental growth / corticotropin-releasing hormone receptor 1 binding / intracellular transport / D1 dopamine receptor binding / Hedgehog 'off' state / beta-2 adrenergic receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / adenylate cyclase activator activity / cellular response to dexamethasone stimulus / trans-Golgi network membrane / female pregnancy / long-term synaptic potentiation / ionotropic glutamate receptor binding / insulin-like growth factor receptor binding / lung development / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / bone development / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G-protein activation / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / hormone activity / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / cognition / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / platelet aggregation / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion

Domain/homology:

GPCR, family 2, corticotropin releasing factor receptor, type 1 / Urocortin/corticotropin-releasing factor / Corticotropin-releasing factor conserved site / Corticotropin-releasing factor family signature. / corticotropin-releasing factor / Corticotropin-releasing factor / GPCR, family 2, corticotropin releasing factor receptor / Corticotropin-releasing factor family / Transducin (heterotrimeric G protein), gamma chain / G Protein Gi Gamma 2 / G-protein coupled receptors family 2 signature 1. / Hormone receptor domain / GPCR, family 2, extracellular hormone receptor domain / G-protein coupled receptors family 2 profile 1. / Domain present in hormone receptors / GPCR family 2, extracellular hormone receptor domain superfamily / G-protein coupled receptors family 2 signature 2. / GPCR, family 2, secretin-like, conserved site / GPCR, family 2, secretin-like / 7 transmembrane receptor (Secretin family) / Rhopdopsin 7-helix transmembrane proteins / Rhodopsin 7-helix transmembrane proteins / GPCR, family 2-like / G-protein coupled receptors family 2 profile 2. / G-protein alpha subunit, group S / YVTN repeat-like/Quinoprotein amine dehydrogenase / 7 Propeller / Methylamine Dehydrogenase; Chain H / G-alpha domain profile. / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G protein alpha subunit / G-protein, gamma subunit / G-protein gamma subunit domain profile. / GGL domain / G-protein gamma-like domain superfamily / G-protein gamma-like domain / GGL domain / G protein gamma subunit-like motifs / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / Few Secondary Structures / Irregular / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / Up-down Bundle / P-loop containing nucleoside triphosphate hydrolase / Mainly Beta / Mainly Alpha

Component:

Corticoliberin / Corticotropin-releasing factor receptor 1 / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(s) subunit alpha isoforms short

• Biological species: Homo sapiens (human); Lama glama (llama)
• Method: ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.91 Å
• Authors: Belousoff, M.J. / Liang, Y.L. / Sexton, P. / Danev, R.

Funding support

Australia, Japan, 5items

Organization	Grant number	Country
National Health and Medical Research Council (Australia)	1120919	Australia
National Health and Medical Research Council (Australia)	1159006	Australia
National Health and Medical Research Council (Australia)	1150083	Australia
Japan Society for the Promotion of Science	KAKENHI #18H06043	Japan
Japan Science and Technology	PRESTO #18069571	Japan

• Citation: Journal: Mol Cell / Year: 2020; Title: Toward a Structural Understanding of Class B GPCR Peptide Binding and Activation.; Authors: Yi-Lynn Liang / Matthew J Belousoff / Peishen Zhao / Cassandra Koole / Madeleine M Fletcher / Tin T Truong / Villy Julita / George Christopoulos / H Eric Xu / Yan Zhang / Maryam Khoshouei / Arthur Christopoulos / Radostin Danev / Patrick M Sexton / Denise Wootten / ; Abstract: Class B G protein-coupled receptors (GPCRs) are important therapeutic targets for major diseases. Here, we present structures of peptide and Gs-bound pituitary adenylate cyclase-activating peptide, PAC1 receptor, and corticotropin-releasing factor (CRF), (CRF1) receptor. Together with recently solved structures, these provide coverage of the major class B GPCR subfamilies. Diverse orientations of the extracellular domain to the receptor core in different receptors are at least partially dependent on evolutionary conservation in the structure and nature of peptide interactions. Differences in peptide interactions to the receptor core also influence the interlinked TM2-TM1-TM6/ECL3/TM7 domain, and this is likely important in their diverse signaling. However, common conformational reorganization of ECL2, linked to reorganization of ICL2, modulates G protein contacts. Comparison between receptors reveals ICL2 as a key domain forming dynamic G protein interactions in a receptor- and ligand-specific manner. This work advances our understanding of class B GPCR activation and Gs coupling.

History

Deposition	Jun 10, 2019	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Feb 5, 2020	Provider: repository / Type: Initial release
Revision 1.1	Feb 12, 2020	Group: Database references / Category: citation / citation_author Item: _citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2	Feb 19, 2020	Group: Database references / Category: citation Item: _citation.journal_volume / _citation.page_first / _citation.page_last