Structure of a nanobody-stabilized active state of the β(2) adrenoceptor
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Nature |
Volume | 469 |
Issue number | 7329 |
Pages (from-to) | 175-80 |
Number of pages | 6 |
ISSN | 0028-0836 |
DOIs | |
Publication status | Published - 13 Jan 2011 |
- Adrenergic beta-2 Receptor Agonists, Animals, Binding Sites, Camelids, New World, Crystallography, X-Ray, Drug Inverse Agonism, Humans, Immunoglobulin Fragments, Ligands, Models, Molecular, Movement, Nanostructures, Opsins, Propanolamines, Protein Conformation, Protein Stability, Receptors, Adrenergic, beta-2, Viral Proteins
Research areas
ID: 120588433