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-Structure paper
Title | Step-wise activation of a Family C GPCR. |
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Journal, issue, pages | bioRxiv, Year 2023 |
Publish date | Aug 30, 2023 |
Authors | Kaavya Krishna Kumar / Haoqing Wang / Chris Habrian / Naomi R Latorraca / Jun Xu / Evan S O'Brien / Chensong Zhang / Elizabeth Montabana / Antoine Koehl / Susan Marqusee / Ehud Y Isacoff / Brian K Kobilka / |
PubMed Abstract | Metabotropic glutamate receptors belong to a family of G protein-coupled receptors that are obligate dimers and possess a large extracellular ligand-binding domain (ECD) that is linked via a cysteine- ...Metabotropic glutamate receptors belong to a family of G protein-coupled receptors that are obligate dimers and possess a large extracellular ligand-binding domain (ECD) that is linked via a cysteine-rich domain (CRDs) to their 7-transmembrane (TM) domain. Upon activation, these receptors undergo a large conformational change to transmit the ligand binding signal from the ECD to the G protein-coupling TM. In this manuscript, we propose a model for a sequential, multistep activation mechanism of metabotropic glutamate receptor subtype 5. We present a series of structures in lipid nanodiscs, from inactive to fully active, including agonist-bound intermediate states. Further, using bulk and single-molecule fluorescence imaging we reveal distinct receptor conformations upon allosteric modulator and G protein binding. |
External links | bioRxiv / PubMed:37693614 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.9 - 3.5 Å |
Structure data | EMDB-41069, PDB-8t6j: EMDB-41092, PDB-8t7h: EMDB-41099, PDB-8t8m: EMDB-41139, PDB-8tao: |
Chemicals | ChemComp-YKU: ChemComp-QUS: |
Source |
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Keywords | SIGNALING PROTEIN / GPCR |