Structural basis for bifunctional peptide recognition at human δ-opioid receptor

Gustavo Fenalti; Nadia Zatsepin; Cecilia Betti; Patrick Giguere; Gye Won Han; Andrii Ishchenko; Wei Liu; Karel Guillemyn; Haitao Zhang; Daniel James; Dingjie Wang; Uwe Weierstall; John Spence; Sébastien Boutet; Marc Messerschmidt; Garth J. Williams; Cornelius Gati; Oleksandr M. Yefanov; Thomas A. White; Dominik Oberthuer; Markus Metz; Chun Hong Yoon; Anton Barty; Henry N. Chapman; Shibom Basu; Jesse Coe; Chelsie E. Conrad; Raimund Fromme; Petra Fromme; Dirk Tourwé; Peter W. Schiller; Bryan L. Roth; Steven Ballet; Vsevolod Katritch; Raymond C. Stevens; Vadim Cherezov

doi:10.1038/nsmb.2965

Structural basis for bifunctional peptide recognition at human δ-opioid receptor

Gustavo Fenalti, Nadia Zatsepin, Cecilia Betti, Patrick Giguere, Gye Won Han, Andrii Ishchenko, Wei Liu, Karel Guillemyn, Haitao Zhang, Daniel James, Dingjie Wang, Uwe Weierstall, John Spence, Sébastien Boutet, Marc Messerschmidt, Garth J. Williams, Cornelius Gati, Oleksandr M. Yefanov, Thomas A. White, Dominik OberthuerMarkus Metz, Chun Hong Yoon, Anton Barty, Henry N. Chapman, Shibom Basu, Jesse Coe, Chelsie E. Conrad, Raimund Fromme, Petra Fromme, Dirk Tourwé, Peter W. Schiller, Bryan L. Roth, Steven Ballet, Vsevolod Katritch, Raymond C. Stevens, Vadim Cherezov

Research output: Contribution to journal › Article › peer-review

145 Scopus citations

Abstract

Bifunctional μ- and δ-opioid receptor (OR) ligands are potential therapeutic alternatives, with diminished side effects, to alkaloid opiate analgesics. We solved the structure of human δ-OR bound to the bifunctional δ-OR antagonist and μ-OR agonist tetrapeptide H-Dmt-Tic-Phe-Phe-NH 2 (DIPP-NH 2) by serial femtosecond crystallography, revealing a cis-peptide bond between H-Dmt and Tic. The observed receptor-peptide interactions are critical for understanding of the pharmacological profiles of opioid peptides and for development of improved analgesics.

Original language	English (US)
Pages (from-to)	265-268
Number of pages	4
Journal	Nature Structural and Molecular Biology
Volume	22
Issue number	3
DOIs	https://doi.org/10.1038/nsmb.2965
State	Published - Mar 6 2015

ASJC Scopus subject areas

Structural Biology
Molecular Biology

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10.1038/nsmb.2965

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Fenalti, G., Zatsepin, N., Betti, C., Giguere, P., Han, G. W., Ishchenko, A., Liu, W., Guillemyn, K., Zhang, H., James, D., Wang, D., Weierstall, U., Spence, J., Boutet, S., Messerschmidt, M., Williams, G. J., Gati, C., Yefanov, O. M., White, T. A., ... Cherezov, V. (2015). Structural basis for bifunctional peptide recognition at human δ-opioid receptor. Nature Structural and Molecular Biology, 22(3), 265-268. https://doi.org/10.1038/nsmb.2965

Fenalti, G, Zatsepin, N, Betti, C, Giguere, P, Han, GW, Ishchenko, A, Liu, W, Guillemyn, K, Zhang, H, James, D, Wang, D, Weierstall, U, Spence, J, Boutet, S, Messerschmidt, M, Williams, GJ, Gati, C, Yefanov, OM, White, TA, Oberthuer, D, Metz, M, Yoon, CH, Barty, A, Chapman, HN, Basu, S, Coe, J, Conrad, CE, Fromme, R , Fromme, P, Tourwé, D, Schiller, PW, Roth, BL, Ballet, S, Katritch, V, Stevens, RC & Cherezov, V 2015, 'Structural basis for bifunctional peptide recognition at human δ-opioid receptor', Nature Structural and Molecular Biology, vol. 22, no. 3, pp. 265-268. https://doi.org/10.1038/nsmb.2965

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abstract = "Bifunctional μ- and δ-opioid receptor (OR) ligands are potential therapeutic alternatives, with diminished side effects, to alkaloid opiate analgesics. We solved the structure of human δ-OR bound to the bifunctional δ-OR antagonist and μ-OR agonist tetrapeptide H-Dmt-Tic-Phe-Phe-NH 2 (DIPP-NH 2) by serial femtosecond crystallography, revealing a cis-peptide bond between H-Dmt and Tic. The observed receptor-peptide interactions are critical for understanding of the pharmacological profiles of opioid peptides and for development of improved analgesics.",

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AU - Oberthuer, Dominik

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AU - Yoon, Chun Hong

AU - Barty, Anton

AU - Chapman, Henry N.

AU - Basu, Shibom

AU - Coe, Jesse

AU - Conrad, Chelsie E.

AU - Fromme, Raimund

AU - Fromme, Petra

AU - Tourwé, Dirk

AU - Schiller, Peter W.

AU - Roth, Bryan L.

AU - Ballet, Steven

AU - Katritch, Vsevolod

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AU - Cherezov, Vadim

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Structural basis for bifunctional peptide recognition at human δ-opioid receptor

Abstract

ASJC Scopus subject areas

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Synchrotron structure of the human delta opioid receptor in complex with a bifunctional peptide (PSI community target)

XFEL structure of the human delta opioid receptor in complex with a bifunctional peptide

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Structural basis for bifunctional peptide recognition at human δ-opioid receptor

Abstract

ASJC Scopus subject areas

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Fingerprint

Datasets

Synchrotron structure of the human delta opioid receptor in complex with a bifunctional peptide (PSI community target)

XFEL structure of the human delta opioid receptor in complex with a bifunctional peptide

Cite this