PDBsum entry 5c1m

Signaling protein/antagonist

PDB id: 5c1m

Contents

Protein chains

296 a.a.

118 a.a.

Ligands

OLC ×2

CLR

PO4

P6G ×2

VF1

Waters ×94

PDB id:

5c1m

Name:

Signaling protein/antagonist

Title:

Crystal structure of active mu-opioid receptor bound to the agonist bu72

Structure:

Mu-type opioid receptor. Chain: a. Synonym: mor-1. Engineered: yes. Nanobody 39. Chain: b. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: oprm1, mor, oprm. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Lama glama. Organism_taxid: 9844. Expressed in: escherichia coli.

Resolution:

2.07Å R-factor: 0.200 R-free: 0.229

Authors:

W.J.Huang,A.Manglik,A.J.Venkatakrishnan,T.Laeremans,E.N.Feinberg, A.L.Sanborn,H.E.Kato,K.E.Livingston,T.S.Thorsen,R.Kling,S.Granier, P.Gmeiner,S.M.Husbands,J.R.Traynor,W.I.Weis,J.Steyaert,R.O.Dror, B.K.Kobilka

Key ref:

W.Huang et al. (2015). Structural insights into µ-opioid receptor activation. Nature, 524, 315-321. PubMed id: 26245379 DOI: 10.1038/nature14886

Date:

15-Jun-15 Release date: 05-Aug-15

Protein chain

P42866  (OPRM_MOUSE) -  Mu-type opioid receptor from Mus musculus

Seq: 398 a.a.

Struc: 296 a.a.*

Protein chain

No UniProt id for this chain

Struc: 118 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1038/nature14886

Nature 524:315-321 (2015)

PubMed id: 26245379

Structural insights into µ-opioid receptor activation.

W.Huang, A.Manglik, A.J.Venkatakrishnan, T.Laeremans, E.N.Feinberg, A.L.Sanborn, H.E.Kato, K.E.Livingston, T.S.Thorsen, R.C.Kling, S.Granier, P.Gmeiner, S.M.Husbands, J.R.Traynor, W.I.Weis, J.Steyaert, R.O.Dror, B.K.Kobilka.

ABSTRACT

Activation of the μ-opioid receptor (μOR) is responsible for the efficacy of the most effective analgesics. To shed light on the structural basis for μOR activation, here we report a 2.1 Å X-ray crystal structure of the murine μOR bound to the morphinan agonist BU72 and a G protein mimetic camelid antibody fragment. The BU72-stabilized changes in the μOR binding pocket are subtle and differ from those observed for agonist-bound structures of the β2-adrenergic receptor (β2AR) and the M2 muscarinic receptor. Comparison with active β2AR reveals a common rearrangement in the packing of three conserved amino acids in the core of the μOR, and molecular dynamics simulations illustrate how the ligand-binding pocket is conformationally linked to this conserved triad. Additionally, an extensive polar network between the ligand-binding pocket and the cytoplasmic domains appears to play a similar role in signal propagation for all three G-protein-coupled receptors.