Structural Insights into β-arrestin/CB1 Receptor Interaction: NMR and CD Studies on Model Peptides
Activation of the cannabinoid CB1 receptor induces different cellular signaling cascades through coupling to different effector proteins (G-proteins and β-arrestins), triggering numerous therapeutic effects. Conformational changes and rearrangements at the intracellular domain of this GPCR receptor...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/21/8111 |
| _version_ | 1797549322763501568 |
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| author | Paula Morales Marta Bruix M. Angeles Jiménez |
| author_facet | Paula Morales Marta Bruix M. Angeles Jiménez |
| author_sort | Paula Morales |
| collection | DOAJ |
| description | Activation of the cannabinoid CB1 receptor induces different cellular signaling cascades through coupling to different effector proteins (G-proteins and β-arrestins), triggering numerous therapeutic effects. Conformational changes and rearrangements at the intracellular domain of this GPCR receptor that accompany ligand binding dictate the signaling pathways. The GPCR-binding interface for G proteins has been extensively studied, whereas β-arrestin/GPCR complexes are still poorly understood. To gain knowledge in this direction, we designed peptides that mimic the motifs involved in the putative interacting region: β-arrestin1 finger loop and the transmembrane helix 7-helix 8 (TMH7-H8) elbow located at the intracellular side of the CB1 receptor. According to circular dichroism and NMR data, these peptides form a native-like, helical conformation and interact with each other in aqueous solution, in the presence of trifluoroethanol, and using zwitterionic detergent micelles as membrane mimics. These results increase our understanding of the binding mode of β-arrestin and CB1 receptor and validate minimalist approaches to structurally comprehend complex protein systems. |
| first_indexed | 2024-03-10T15:13:03Z |
| format | Article |
| id | doaj.art-81c4ebb2daf542b295be1176f25b0b4e |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:13:03Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-81c4ebb2daf542b295be1176f25b0b4e2023-11-20T19:11:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012121811110.3390/ijms21218111Structural Insights into β-arrestin/CB1 Receptor Interaction: NMR and CD Studies on Model PeptidesPaula Morales0Marta Bruix1M. Angeles Jiménez2Departamento de Química Física Biológica, Instituto de Química Física Rocasolano (IQFR-CSIC), Serrano 119, 28006 Madrid, SpainDepartamento de Química Física Biológica, Instituto de Química Física Rocasolano (IQFR-CSIC), Serrano 119, 28006 Madrid, SpainDepartamento de Química Física Biológica, Instituto de Química Física Rocasolano (IQFR-CSIC), Serrano 119, 28006 Madrid, SpainActivation of the cannabinoid CB1 receptor induces different cellular signaling cascades through coupling to different effector proteins (G-proteins and β-arrestins), triggering numerous therapeutic effects. Conformational changes and rearrangements at the intracellular domain of this GPCR receptor that accompany ligand binding dictate the signaling pathways. The GPCR-binding interface for G proteins has been extensively studied, whereas β-arrestin/GPCR complexes are still poorly understood. To gain knowledge in this direction, we designed peptides that mimic the motifs involved in the putative interacting region: β-arrestin1 finger loop and the transmembrane helix 7-helix 8 (TMH7-H8) elbow located at the intracellular side of the CB1 receptor. According to circular dichroism and NMR data, these peptides form a native-like, helical conformation and interact with each other in aqueous solution, in the presence of trifluoroethanol, and using zwitterionic detergent micelles as membrane mimics. These results increase our understanding of the binding mode of β-arrestin and CB1 receptor and validate minimalist approaches to structurally comprehend complex protein systems.https://www.mdpi.com/1422-0067/21/21/8111CB1β-arrestin1NMRCircular dichroismGPCR |
| spellingShingle | Paula Morales Marta Bruix M. Angeles Jiménez Structural Insights into β-arrestin/CB1 Receptor Interaction: NMR and CD Studies on Model Peptides International Journal of Molecular Sciences CB1 β-arrestin1 NMR Circular dichroism GPCR |
| title | Structural Insights into β-arrestin/CB1 Receptor Interaction: NMR and CD Studies on Model Peptides |
| title_full | Structural Insights into β-arrestin/CB1 Receptor Interaction: NMR and CD Studies on Model Peptides |
| title_fullStr | Structural Insights into β-arrestin/CB1 Receptor Interaction: NMR and CD Studies on Model Peptides |
| title_full_unstemmed | Structural Insights into β-arrestin/CB1 Receptor Interaction: NMR and CD Studies on Model Peptides |
| title_short | Structural Insights into β-arrestin/CB1 Receptor Interaction: NMR and CD Studies on Model Peptides |
| title_sort | structural insights into β arrestin cb1 receptor interaction nmr and cd studies on model peptides |
| topic | CB1 β-arrestin1 NMR Circular dichroism GPCR |
| url | https://www.mdpi.com/1422-0067/21/21/8111 |
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