5C1M

Crystal structure of active mu-opioid receptor bound to the agonist BU72

Summary for 5C1M

• Entry DOI: 10.2210/pdb5c1m/pdb
• Related: 4DKL
• Descriptor: Mu-type opioid receptor, Nanobody 39, (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate, ... (8 entities in total)
• Functional Keywords: ligands, mice, agonists, morphinans, activation, receptors, opioid, mu, nanobody, signaling protein-antagonist complex, signaling protein/antagonist
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 2
• Total formula weight: 49585.21

Authors

Huang, W.J.,Manglik, A.,Venkatakrishnan, A.J.,Laeremans, T.,Feinberg, E.N.,Sanborn, A.L.,Kato, H.E.,Livingston, K.E.,Thorsen, T.S.,Kling, R.,Granier, S.,Gmeiner, P.,Husbands, S.M.,Traynor, J.R.,Weis, W.I.,Steyaert, J.,Dror, R.O.,Kobilka, B.K. (deposition date: 2015-06-15, release date: 2015-08-05, Last modification date: 2023-09-27)

Primary citation

Huang, W.,Manglik, A.,Venkatakrishnan, A.J.,Laeremans, T.,Feinberg, E.N.,Sanborn, A.L.,Kato, H.E.,Livingston, K.E.,Thorsen, T.S.,Kling, R.C.,Granier, S.,Gmeiner, P.,Husbands, S.M.,Traynor, J.R.,Weis, W.I.,Steyaert, J.,Dror, R.O.,Kobilka, B.K.
Structural insights into mu-opioid receptor activation.
Nature, 524:315-321, 2015

PubMed 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.

PubMed: 26245379
DOI: 10.1038/nature14886

Experimental method

X-RAY DIFFRACTION (2.07 Å)