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8BV5

Focus refinement of soluble domain of Adenylyl cyclase 8 bound to stimulatory G protein, Forskolin, ATPalphaS, and Ca2+/Calmodulin in lipid nanodisc conditions

8BV5 の概要
エントリーDOI10.2210/pdb8bv5/pdb
EMDBエントリー16249 16255
分子名称Adenylate cyclase type 8, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, FORSKOLIN, ... (5 entities in total)
機能のキーワードadenylyl cyclase, camp signaling, g proteins, calmodulin, membrane protein
由来する生物種Bos taurus (cattle)
詳細
タンパク質・核酸の鎖数2
化学式量合計188170.18
構造登録者
Khanppnavar, B.,Korkhov, V.M. (登録日: 2023-01-04, 公開日: 2024-01-17, 最終更新日: 2024-11-20)
主引用文献Khanppnavar, B.,Schuster, D.,Lavriha, P.,Uliana, F.,Ozel, M.,Mehta, V.,Leitner, A.,Picotti, P.,Korkhov, V.M.
Regulatory sites of CaM-sensitive adenylyl cyclase AC8 revealed by cryo-EM and structural proteomics.
Embo Rep., 25:1513-1540, 2024
Cited by
PubMed Abstract: Membrane adenylyl cyclase AC8 is regulated by G proteins and calmodulin (CaM), mediating the crosstalk between the cAMP pathway and Ca signalling. Despite the importance of AC8 in physiology, the structural basis of its regulation by G proteins and CaM is not well defined. Here, we report the 3.5 Å resolution cryo-EM structure of the bovine AC8 bound to the stimulatory Gαs protein in the presence of Ca/CaM. The structure reveals the architecture of the ordered AC8 domains bound to Gαs and the small molecule activator forskolin. The extracellular surface of AC8 features a negatively charged pocket, a potential site for unknown interactors. Despite the well-resolved forskolin density, the captured state of AC8 does not favour tight nucleotide binding. The structural proteomics approaches, limited proteolysis and crosslinking mass spectrometry (LiP-MS and XL-MS), allowed us to identify the contact sites between AC8 and its regulators, CaM, Gαs, and Gβγ, as well as to infer the conformational changes induced by these interactions. Our results provide a framework for understanding the role of flexible regions in the mechanism of AC regulation.
PubMed: 38351373
DOI: 10.1038/s44319-024-00076-y
主引用文献が同じPDBエントリー
実験手法
ELECTRON MICROSCOPY (3.54 Å)
構造検証レポート
Validation report summary of 8bv5
検証レポート(詳細版)ダウンロードをダウンロード

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件を2025-07-23に公開中

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