8DPG

Cryo-EM structure of the 5HT2C receptor (INI isoform) bound to psilocin

8DPG の概要

• エントリーDOI: 10.2210/pdb8dpg/pdb
• EMDBエントリー: 27634
• 分子名称: 5-hydroxytryptamine receptor 2C, G-alpha subunit q (Gi2-mini-Gq chimera), Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (7 entities in total)
• 機能のキーワード: gpcr, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 156499.97

構造登録者

Gumpper, R.H.,Fay, J.F.,Roth, B.L. (登録日: 2022-07-15, 公開日: 2022-08-24, 最終更新日: 2025-05-14)

主引用文献

Gumpper, R.H.,Fay, J.F.,Roth, B.L.
Molecular insights into the regulation of constitutive activity by RNA editing of 5HT 2C serotonin receptors.
Cell Rep, 40:111211-111211, 2022

PubMed Abstract: RNA editing is a process by which post-transcriptional changes of mRNA nucleotides alter protein function through modification of the amino acid content. The 5HT serotonin receptor, which undergoes 32 distinct RNA-editing events leading to 24 protein isoforms, is a notable example of this process. These 5HT isoforms display differences in constitutive activity, agonist/inverse agonist potencies, and efficacies. To elucidate the molecular mechanisms responsible for these effects of RNA editing, we present four active-state 5HT-transducer-coupled structures of three representative isoforms (INI, VGV, and VSV) with the selective drug lorcaserin (Belviq) and the classic psychedelic psilocin. We also provide a comprehensive analysis of agonist activation and constitutive activity across all 24 protein isoforms. Collectively, these findings reveal a unique hydrogen-bonding network located on intracellular loop 2 that is subject to RNA editing, which differentially affects GPCR constitutive and agonist signaling activities.

PubMed: 35977511
DOI: 10.1016/j.celrep.2022.111211

実験手法

ELECTRON MICROSCOPY (3.6 Å)