PDBsum entry 6h7m

Immune system

PDB id: 6h7m

Contents

Protein chains

107 a.a.

291 a.a.

120 a.a.

Ligands

2CV ×7

68H ×2

Metals

_NA ×2

Waters ×13

PDB id:

6h7m

Name:

Immune system

Title:

Activated turkey beta1 adrenoceptor with bound partial agonist salbutamol and nanobody nb6b9

Structure:

Thioredoxin 1. Chain: e, f. Synonym: trx-1. Engineered: yes. Mutation: yes. Beta-1 adrenergic receptor. Chain: a, b. Synonym: beta-1 adrenoreceptor,beta-t. Engineered: yes.

Source:

Escherichia coli (strain k12). Organism_taxid: 83333. Strain: k12. Gene: trxa, fipa, tsnc, b3781, jw5856. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Meleagris gallopavo. Wild turkey. Organism_taxid: 9103.

Resolution:

2.76Å R-factor: 0.266 R-free: 0.285

Authors:

T.Warne,P.C.Edwards,A.S.Dore,A.G.W.Leslie,C.G.Tate

Key ref:

T.Warne et al. (2019). Molecular basis for high-affinity agonist binding in GPCRs. Science, 364, 775-778. PubMed id: 31072904 DOI: 10.1126/science.aau5595

Date:

31-Jul-18 Release date: 17-Oct-18

Protein chains

P0AA25  (THIO_ECOLI) -  Thioredoxin 1 from Escherichia coli (strain K12)

Seq: 109 a.a.

Struc: 107 a.a.*

Protein chains

P07700  (ADRB1_MELGA) -  Beta-1 adrenergic receptor from Meleagris gallopavo

Seq: 483 a.a.

Struc: 291 a.a.*

Protein chains

No UniProt id for this chain

Struc: 120 a.a.

* PDB and UniProt seqs differ at 13 residue positions (black crosses)

DOI no: 10.1126/science.aau5595

Science 364:775-778 (2019)

PubMed id: 31072904

Molecular basis for high-affinity agonist binding in GPCRs.

T.Warne, P.C.Edwards, A.S.Doré, A.G.W.Leslie, C.G.Tate.

ABSTRACT

G protein-coupled receptors (GPCRs) in the G protein-coupled active state have higher affinity for agonists as compared with when they are in the inactive state, but the molecular basis for this is unclear. We have determined four active-state structures of the β₁-adrenoceptor (β₁AR) bound to conformation-specific nanobodies in the presence of agonists of varying efficacy. Comparison with inactive-state structures of β₁AR bound to the identical ligands showed a 24 to 42% reduction in the volume of the orthosteric binding site. Potential hydrogen bonds were also shorter, and there was up to a 30% increase in the number of atomic contacts between the receptor and ligand. This explains the increase in agonist affinity of GPCRs in the active state for a wide range of structurally distinct agonists.