PDBsum entry 4z9g

Signaling protein

PDB id: 4z9g

Contents

Protein chains

421 a.a.

Ligands

OLA ×10

1Q5 ×3

SO4 ×3

PDB id:

4z9g

Name:

Signaling protein

Title:

Crystal structure of human corticotropin-releasing factor receptor 1 (crf1r) in complex with the antagonist cp-376395 in a hexagonal setting with translational non-crystallographic symmetry

Structure:

Corticotropin-releasing factor receptor 1,lysozyme, corticotropin-releasing factor receptor 1. Chain: a, b, c. Synonym: crfr-1,corticotropin-releasing hormone receptor 1. Engineered: yes. Mutation: yes. Other_details: corticotropin-releasing factor receptor 1, t4-lysozyme chimeric construct

Source:

Homo sapiens, enterobacteria phage rb51. Human. Organism_taxid: 9606, 10693. Gene: crhr1, crfr, crfr1, crhr, e, rb51orf131. Expressed in: trichoplusia ni. Expression_system_taxid: 7111.

Resolution:

3.18Å R-factor: 0.247 R-free: 0.289

Authors:

A.S.Dore,A.Bortolato,K.Hollenstein,R.K.Y.Cheng,R.J.Read,F.H.Marshall

Key ref:

A.S.Dore et al. (2017). Decoding Corticotropin-Releasing Factor Receptor Type 1 Crystal Structures. Curr Mol Pharmacol, 10, 334-344. PubMed id: 28183242

Date:

10-Apr-15 Release date: 29-Jun-16

Protein chains

C3V2B5  (C3V2B5_BPR51) -  Endolysin from Enterobacteria phage RB51

Seq: 164 a.a.

Struc: 421 a.a.*

Protein chains

P34998  (CRFR1_HUMAN) -  Corticotropin-releasing factor receptor 1 from Homo sapiens

Seq: 415 a.a.

Struc: 421 a.a.*

* PDB and UniProt seqs differ at 177 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.2.1.17 - lysozyme.
• Reaction: Hydrolysis of the 1,4-beta-linkages between N-acetyl-D-glucosamine and N-acetylmuramic acid in peptidoglycan heteropolymers of the prokaryotes cell walls.

Curr Mol Pharmacol 10:334-344 (2017)

PubMed id: 28183242

Decoding Corticotropin-Releasing Factor Receptor Type 1 Crystal Structures.

A.S.Dore, A.Bortolato, K.Hollenstein, R.K.Y.Cheng, R.J.Read, F.H.Marshall.

ABSTRACT

The structural analysis of class B G protein-coupled receptors (GPCR), cell surface proteins responding to peptide hormones, has until recently been restricted to the extracellular domain (ECD). Corticotropin-releasing factor receptor type 1 (CRF1R) is a class B receptor mediating stress response and also considered a drug target for depression and anxiety. Here we report the crystal structure of the transmembrane domain of human CRF1R in complex with the small-molecule antagonist CP-376395 in a hexagonal setting with translational non-crystallographic symmetry. Molecular dynamics and metadynamics simulations on this novel structure and the existing TMD structure for CRF1R provides insight as to how the small molecule ligand gains access to the induced-fit allosteric binding site with implications for the observed selectivity against CRF2R. Furthermore, molecular dynamics simulations performed using a full-length receptor model point to key interactions between the ECD and extracellular loop 3 of the TMD providing insight into the full inactive state of multidomain class B GPCRs.