Nature Communications (Feb 2021)
Structures of active-state orexin receptor 2 rationalize peptide and small-molecule agonist recognition and receptor activation
- Chuan Hong,
- Noel J. Byrne,
- Beata Zamlynny,
- Srivanya Tummala,
- Li Xiao,
- Jennifer M. Shipman,
- Andrea T. Partridge,
- Christina Minnick,
- Michael J. Breslin,
- Michael T. Rudd,
- Shawn J. Stachel,
- Vanessa L. Rada,
- Jeffrey C. Kern,
- Kira A. Armacost,
- Scott A. Hollingsworth,
- Julie A. O’Brien,
- Dawn L. Hall,
- Terrence P. McDonald,
- Corey Strickland,
- Alexei Brooun,
- Stephen M. Soisson,
- Kaspar Hollenstein
Affiliations
- Chuan Hong
- Computational & Structural Chemistry, MRL, Merck & Co., Inc
- Noel J. Byrne
- Computational & Structural Chemistry, MRL, Merck & Co., Inc
- Beata Zamlynny
- Screening & Compound Profiling, MRL, Merck & Co., Inc
- Srivanya Tummala
- Computational & Structural Chemistry, MRL, Merck & Co., Inc
- Li Xiao
- Computational & Structural Chemistry, MRL, Merck & Co., Inc
- Jennifer M. Shipman
- Computational & Structural Chemistry, MRL, Merck & Co., Inc
- Andrea T. Partridge
- Computational & Structural Chemistry, MRL, Merck & Co., Inc
- Christina Minnick
- Quantitative Bioscience, MRL, Merck & Co., Inc
- Michael J. Breslin
- Discovery Chemistry, MRL, Merck & Co., Inc
- Michael T. Rudd
- Discovery Chemistry, MRL, Merck & Co., Inc
- Shawn J. Stachel
- Discovery Chemistry, MRL, Merck & Co., Inc
- Vanessa L. Rada
- Discovery Chemistry, MRL, Merck & Co., Inc
- Jeffrey C. Kern
- Discovery Chemistry, MRL, Merck & Co., Inc
- Kira A. Armacost
- Computational & Structural Chemistry, MRL, Merck & Co., Inc
- Scott A. Hollingsworth
- Computational & Structural Chemistry, MRL, Merck & Co., Inc.
- Julie A. O’Brien
- Quantitative Bioscience, MRL, Merck & Co., Inc
- Dawn L. Hall
- Computational & Structural Chemistry, MRL, Merck & Co., Inc
- Terrence P. McDonald
- Neuroscience, MRL, Merck & Co., Inc
- Corey Strickland
- Computational & Structural Chemistry, MRL, Merck & Co., Inc
- Alexei Brooun
- Computational & Structural Chemistry, MRL, Merck & Co., Inc
- Stephen M. Soisson
- Computational & Structural Chemistry, MRL, Merck & Co., Inc
- Kaspar Hollenstein
- Computational & Structural Chemistry, MRL, Merck & Co., Inc
- DOI
- https://doi.org/10.1038/s41467-021-21087-6
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 11
Abstract
Agonists of the orexin receptor 2 (OX2R) show promise in the treatment of narcolepsy. Cryo-EM structures of active-state OX2R bound to an endogenous peptide agonist and a small-molecule agonist suggest a molecular mechanism that rationalizes both receptor activation and inhibition.
