6H7J

ACTIVATED TURKEY BETA1 ADRENOCEPTOR WITH BOUND AGONIST ISOPRENALINE AND NANOBODY Nb80

PDB DOI: https://doi.org/10.2210/pdb6H7J/pdb

Classification: IMMUNE SYSTEM
Organism(s): Escherichia coli K-12, Meleagris gallopavo, Lama glama
Expression System: Trichoplusia ni, Escherichia coli
Mutation(s): Yes
Membrane Protein: Yes OPMPDBTMMemProtMDmpstruc

Deposited: 2018-07-31 Released: 2018-10-17
Deposition Author(s): Warne, T., Edwards, P.C., Dore, A.S., Leslie, A.G.W., Tate, C.G.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.80 ?
R-Value Free: 0.317
R-Value Work: 0.285
R-Value Observed: 0.286

Starting Models: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.6 of the entry. See complete history.

Literature

Molecular basis for high-affinity agonist binding in GPCRs.

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

(2019) Science 364: 775-778

PubMed: 31072904 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1126/science.aau5595
Primary Citation of Related Structures:
6H7J, 6H7L, 6H7M, 6H7O

PubMed 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 β ₁-adrenoceptor (β ₁AR) bound to conformation-specific nanobodies in the presence of agonists of varying efficacy. Comparison with inactive-state structures of β ₁AR 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.

Organizational Affiliation

Medical Research Council (MRC) Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.

Macromolecule Content

Total Structure Weight: 122.02 kDa
Atom Count: 8,094
Modelled Residue Count: 1,021
Deposited Residue Count: 1,074
Unique protein chains: 3

Macromolecules

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Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Thioredoxin 1	A [auth E], D [auth F]	109	Escherichia coli K-12	Mutation(s): 2 Gene Names: trxA, fipA, tsnC, b3781, JW5856
UniProt
Find proteins for P0AA25 (Escherichia coli (strain K12)) Explore P0AA25 Go to UniProtKB: P0AA25
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P0AA25
Sequence Annotations Expand
Reference Sequence

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Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
Beta-1 adrenergic receptor	B [auth A], E [auth B]	307	Meleagris gallopavo	Mutation(s): 6 Gene Names: ADRB1 Membrane Entity: Yes
UniProt
Find proteins for P07700 (Meleagris gallopavo) Explore P07700 Go to UniProtKB: P07700
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P07700
Sequence Annotations Expand
Reference Sequence

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(by identity cutoff) | 3D Structure

Entity ID: 3
Molecule	Chains	Sequence Length	Organism	Details	Image
Camelid antibody fragment Nb80	C, F [auth D]	121	Lama glama	Mutation(s): 0
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
2CV Query on 2CV Download Ideal Coordinates CCD File SDF format, chain I [auth A] SDF format, chain J [auth A] SDF format, chain K [auth A] SDF format, chain L [auth B] SDF format, chain O [auth B] MOL2 format, chain I [auth A] MOL2 format, chain J [auth A] MOL2 format, chain K [auth A] MOL2 format, chain L [auth B] MOL2 format, chain O [auth B] mmCIF format, chain I [auth A] mmCIF format, chain J [auth A] mmCIF format, chain K [auth A] mmCIF format, chain L [auth B] mmCIF format, chain O [auth B]	I [auth A], J [auth A], K [auth A], L [auth B], O [auth B]	HEGA-10 C₁₈ H₃₇ N O₇ ITEIKACYSCODFV-ATLSCFEFSA-N		Interactions Focus chain I [auth A] Focus chain J [auth A] Focus chain K [auth A] Focus chain L [auth B] Focus chain O [auth B] Interactions & Density Focus chain I [auth A] Focus chain J [auth A] Focus chain K [auth A] Focus chain L [auth B] Focus chain O [auth B]
5FW Query on 5FW Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain M [auth B] MOL2 format, chain G [auth A] MOL2 format, chain M [auth B] mmCIF format, chain G [auth A] mmCIF format, chain M [auth B]	G [auth A], M [auth B]	ISOPRENALINE C₁₁ H₁₇ N O₃ JWZZKOKVBUJMES-NSHDSACASA-N		Interactions Focus chain G [auth A] Focus chain M [auth B] Interactions & Density Focus chain G [auth A] Focus chain M [auth B]
NA Query on NA Download Ideal Coordinates CCD File SDF format, chain H [auth A] SDF format, chain N [auth B] MOL2 format, chain H [auth A] MOL2 format, chain N [auth B] mmCIF format, chain H [auth A] mmCIF format, chain N [auth B]	H [auth A], N [auth B]	SODIUM ION Na FKNQFGJONOIPTF-UHFFFAOYSA-N		Interactions Focus chain H [auth A] Focus chain N [auth B] Interactions & Density Focus chain H [auth A] Focus chain N [auth B]