5WF5

Agonist bound human A2a adenosine receptor with D52N mutation at 2.60 A resolution

5WF5 の概要

• エントリーDOI: 10.2210/pdb5wf5/pdb
• 分子名称: Human A2a adenosine receptor T4L chimera, 6-(2,2-diphenylethylamino)-9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxy-oxolan-2-yl]-N-[2-[(1-pyridin-2-ylpiperidin-4-yl)carbamoylamino]ethyl]purine-2-carboxamide, (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate, ... (4 entities in total)
• 機能のキーワード: human a2a adenosine receptor, d52n, gpcr-t4l chimera, membrane protein, lcp, agonist, uk432097, activation microswitch, allosteric na-site mutant, gpcr signaling
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cell membrane; Multi-pass membrane protein: P29274
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 58046.03

構造登録者

White, K.L.,Eddy, M.T.,Gao, Z.,Han, G.W.,Hanson, M.A.,Lian, T.,Deary, A.,Patel, N.,Jacobson, K.A.,Katritch, V.,Stevens, R.C. (登録日: 2017-07-11, 公開日: 2018-02-21, 最終更新日: 2024-10-16)

主引用文献

White, K.L.,Eddy, M.T.,Gao, Z.G.,Han, G.W.,Lian, T.,Deary, A.,Patel, N.,Jacobson, K.A.,Katritch, V.,Stevens, R.C.
Structural Connection between Activation Microswitch and Allosteric Sodium Site in GPCR Signaling.
Structure, 26:259-269.e5, 2018

PubMed Abstract: Sodium 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 A adenosine receptor, D52N and S91A. 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 DN variant is a promising method for stabilizing class A GPCRs to accelerate structural efforts and drug discovery.

PubMed: 29395784
DOI: 10.1016/j.str.2017.12.013

実験手法

X-RAY DIFFRACTION (2.6 Å)