7p2l | pdb_00007p2l
thermostabilised 7TM domain of human mGlu5 receptor bound to photoswitchable ligand alloswitch-1
Structural highlights
FunctionENLYS_BPT4 Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles. Once the holin has permeabilized the host cell membrane, the endolysin can reach the periplasm and break down the peptidoglycan layer.[1] GRM5_HUMAN Receptor for glutamate. The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger system and generates a calcium-activated chloride current. Publication Abstract from PubMedMetabotropic glutamate receptors (mGluRs) are dimeric G-protein-coupled receptors activated by the main excitatory neurotransmitter, L-glutamate. mGluR activation by agonists binding in the venus flytrap domain is regulated by positive (PAM) or negative (NAM) allosteric modulators binding to the 7-transmembrane domain (7TM). We report the cryo-electron microscopy structures of fully inactive and intermediate-active conformations of mGlu5 receptor bound to an antagonist and a NAM or an agonist and a PAM, respectively, as well as the crystal structure of the 7TM bound to a photoswitchable NAM. The agonist induces a large movement between the subunits, bringing the 7TMs together and stabilizing a 7TM conformation structurally similar to the inactive state. Using functional approaches, we demonstrate that the PAM stabilizes a 7TM active conformation independent of the conformational changes induced by agonists, representing an alternative mode of mGlu activation. These findings provide a structural basis for different mGluR activation modes. Agonists and allosteric modulators promote signaling from different metabotropic glutamate receptor 5 conformations.,Nasrallah C, Cannone G, Briot J, Rottier K, Berizzi AE, Huang CY, Quast RB, Hoh F, Baneres JL, Malhaire F, Berto L, Dumazer A, Font-Ingles J, Gomez-Santacana X, Catena J, Kniazeff J, Goudet C, Llebaria A, Pin JP, Vinothkumar KR, Lebon G Cell Rep. 2021 Aug 31;36(9):109648. doi: 10.1016/j.celrep.2021.109648. PMID:34469715[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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