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GPCR SIGNALING

Feeling at home: Structure of the NTSR1–Gi complex in a lipid environment

The interaction of G protein–coupled receptors (GPCRs) with heterotrimeric G proteins plays a critical role in signal transduction processes, and multiple GPCR–G protein complexes reconstituted in detergent micelles have been visualized using cryo-EM. A new study reports the structure of neurotensin receptor 1 (NTSR1) in complex with the heterotrimeric Gi protein, assembled in a lipid environment using circularized nanodiscs. The structure sheds light on how the lipid context may influence receptor–G protein coupling and activation.

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Fig. 1: Cryo-EM analysis of the NTSR1–Gi complex reveals two conformational states.
Fig. 2: An overall comparison of the NTSR1–Gi structure with structures of the DRD2–Gi and NTSR1–βarr1 complexes.

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Acknowledgements

This work is supported by a Senior Fellowship of the DBT Wellcome Trust India Alliance (IA/S/20/1/504916) awarded to A.K.S. and the SERB National Facility for Cryo-Electron Microscopy at IIT Kanpur (IPA/2020/000405). A.K.S. is an EMBO Young Investigator and Joy Gill Chair professor.

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Correspondence to Arun K. Shukla.

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Maharana, J., Shukla, A.K. Feeling at home: Structure of the NTSR1–Gi complex in a lipid environment. Nat Struct Mol Biol 28, 331–333 (2021). https://doi.org/10.1038/s41594-021-00581-x

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