Structure of a nanobody-stabilized active state of the β(2) adrenoceptor

Nature. 2011 Jan 13;469(7329):175-80. doi: 10.1038/nature09648.


G protein coupled receptors (GPCRs) exhibit a spectrum of functional behaviours in response to natural and synthetic ligands. Recent crystal structures provide insights into inactive states of several GPCRs. Efforts to obtain an agonist-bound active-state GPCR structure have proven difficult due to the inherent instability of this state in the absence of a G protein. We generated a camelid antibody fragment (nanobody) to the human β(2) adrenergic receptor (β(2)AR) that exhibits G protein-like behaviour, and obtained an agonist-bound, active-state crystal structure of the receptor-nanobody complex. Comparison with the inactive β(2)AR structure reveals subtle changes in the binding pocket; however, these small changes are associated with an 11 Å outward movement of the cytoplasmic end of transmembrane segment 6, and rearrangements of transmembrane segments 5 and 7 that are remarkably similar to those observed in opsin, an active form of rhodopsin. This structure provides insights into the process of agonist binding and activation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-2 Receptor Agonists / chemistry*
  • Adrenergic beta-2 Receptor Agonists / immunology
  • Adrenergic beta-2 Receptor Agonists / metabolism
  • Adrenergic beta-2 Receptor Agonists / pharmacology*
  • Animals
  • Binding Sites
  • Camelids, New World
  • Crystallography, X-Ray
  • Drug Inverse Agonism
  • Humans
  • Immunoglobulin Fragments / chemistry*
  • Immunoglobulin Fragments / immunology*
  • Immunoglobulin Fragments / metabolism
  • Immunoglobulin Fragments / pharmacology
  • Ligands
  • Models, Molecular
  • Movement / drug effects
  • Nanostructures / chemistry*
  • Opsins / agonists
  • Opsins / chemistry
  • Opsins / metabolism
  • Propanolamines / chemistry
  • Propanolamines / metabolism
  • Propanolamines / pharmacology
  • Protein Conformation / drug effects
  • Protein Stability / drug effects
  • Receptors, Adrenergic, beta-2 / chemistry*
  • Receptors, Adrenergic, beta-2 / metabolism*
  • Viral Proteins / chemistry
  • Viral Proteins / metabolism


  • Adrenergic beta-2 Receptor Agonists
  • Immunoglobulin Fragments
  • Ligands
  • Opsins
  • Propanolamines
  • Receptors, Adrenergic, beta-2
  • Viral Proteins
  • gene 5 protein, Enterobacteria phage T4
  • carazolol

Associated data

  • PDB/3P0G