6N4Y

Metabotropic Glutamate Receptor 5 Extracellular Domain with Nb43

Summary for 6N4Y

• Entry DOI: 10.2210/pdb6n4y/pdb
• Descriptor: Metabotropic glutamate receptor 5, Nanobody 43, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: cell surface receptor nanobody, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 327595.49

Authors

Koehl, A.,Hu, H.,Feng, D.,Sun, B.,Chu, M.,Weis, W.I.,Mathiesen, J.M.,Skiniotis, G.,Kobilka, B.K. (deposition date: 2018-11-20, release date: 2019-01-23, Last modification date: 2024-11-06)

Primary citation

Koehl, A.,Hu, H.,Feng, D.,Sun, B.,Zhang, Y.,Robertson, M.J.,Chu, M.,Kobilka, T.S.,Laermans, T.,Steyaert, J.,Tarrasch, J.,Dutta, S.,Fonseca, R.,Weis, W.I.,Mathiesen, J.M.,Skiniotis, G.,Kobilka, B.K.
Structural insights into the activation of metabotropic glutamate receptors.
Nature, 566:79-84, 2019

PubMed Abstract: Metabotropic glutamate receptors are family C G-protein-coupled receptors. They form obligate dimers and possess extracellular ligand-binding Venus flytrap domains, which are linked by cysteine-rich domains to their 7-transmembrane domains. Spectroscopic studies show that signalling is a dynamic process, in which large-scale conformational changes underlie the transmission of signals from the extracellular Venus flytraps to the G protein-coupling domains-the 7-transmembrane domains-in the membrane. Here, using a combination of X-ray crystallography, cryo-electron microscopy and signalling studies, we present a structural framework for the activation mechanism of metabotropic glutamate receptor subtype 5. Our results show that agonist binding at the Venus flytraps leads to a compaction of the intersubunit dimer interface, thereby bringing the cysteine-rich domains into close proximity. Interactions between the cysteine-rich domains and the second extracellular loops of the receptor enable the rigid-body repositioning of the 7-transmembrane domains, which come into contact with each other to initiate signalling.

PubMed: 30675062
DOI: 10.1038/s41586-019-0881-4

Experimental method

X-RAY DIFFRACTION (3.262 Å)