5wf5
From Proteopedia
Agonist bound human A2a adenosine receptor with D52N mutation at 2.60 A resolution
Structural highlights
FunctionAA2AR_HUMAN Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.ENLYS_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] Publication Abstract from PubMedSodium ions are endogenous allosteric modulators of many G-protein-coupled receptors (GPCRs). Mutation of key residues in the sodium binding motif causes a striking effect on G-protein signaling. We report the crystal structures of agonist complexes for two variants in the first sodium coordination shell of the human A2A adenosine receptor, D52(2.50)N and S91(3.39)A. Both structures present an overall active-like conformation; however, the variants show key changes in the activation motif NPxxY. Changes in the hydrogen bonding network in this microswitch suggest a possible mechanism for modified G-protein signaling and enhanced thermal stability. These structures, signaling data, and thermal stability analysis with a panel of pharmacological ligands provide a basis for understanding the role of the sodium-coordinating residues on stability and G-protein signaling. Utilizing the D(2.50)N variant is a promising method for stabilizing class A GPCRs to accelerate structural efforts and drug discovery. Structural Connection between Activation Microswitch and Allosteric Sodium Site in GPCR Signaling.,White KL, Eddy MT, Gao ZG, Han GW, Lian T, Deary A, Patel N, Jacobson KA, Katritch V, Stevens RC Structure. 2018 Feb 6;26(2):259-269.e5. doi: 10.1016/j.str.2017.12.013. Epub 2018, Jan 27. PMID:29395784[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Escherichia virus T4 | Homo sapiens | Large Structures | Deary A | Eddy MT | Gao Z | Han GW | Hanson MA | Jacobson KA | Katritch V | Lian T | Patel N | Stevens RC | White KL
