- EMDB-16255: Focus refinement of soluble domain of Adenylyl cyclase 8 bound to... -
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基本情報
登録情報
データベース: EMDB / ID: EMD-16255
タイトル
Focus refinement of soluble domain of Adenylyl cyclase 8 bound to stimulatory G protein, Forskolin, ATPalphaS, and Ca2+/Calmodulin in lipid nanodisc conditions
マップデータ
試料
複合体: Structure of Adenylyl cyclase 8 bound to stimulatory G protein, Forskolin, ATPalphaS, and Ca2+/Calmodulin in lipid nanodisc
複合体: Adenylyl Cyclase 8
タンパク質・ペプチド: Adenylate cyclase type 8
複合体: G protein alpha S
タンパク質・ペプチド: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
複合体: Calmodulin
リガンド: FORSKOLIN
リガンド: 5'-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE
リガンド: MAGNESIUM ION
キーワード
Adenylyl Cyclase / cAMP signaling / G proteins / Calmodulin / MEMBRANE PROTEIN
機能・相同性
機能・相同性情報
cellular response to morphine / Adenylate cyclase activating pathway / Adenylate cyclase inhibitory pathway / positive regulation of long-term synaptic depression / glucose mediated signaling pathway / calcium- and calmodulin-responsive adenylate cyclase activity / regulation of cellular response to stress / PKA activation / neuroinflammatory response / sensory perception of chemical stimulus ...cellular response to morphine / Adenylate cyclase activating pathway / Adenylate cyclase inhibitory pathway / positive regulation of long-term synaptic depression / glucose mediated signaling pathway / calcium- and calmodulin-responsive adenylate cyclase activity / regulation of cellular response to stress / PKA activation / neuroinflammatory response / sensory perception of chemical stimulus / adenylate cyclase / positive regulation of synaptic plasticity / Hedgehog 'off' state / cAMP biosynthetic process / adenylate cyclase activity / G alpha (z) signalling events / neuronal cell body membrane / cellular response to glucagon stimulus / presynaptic active zone / positive regulation of insulin secretion involved in cellular response to glucose stimulus / excitatory synapse / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / D1 dopamine receptor binding / long-term memory / beta-2 adrenergic receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / regulation of cytosolic calcium ion concentration / adenylate cyclase activator activity / hippocampal mossy fiber to CA3 synapse / positive regulation of long-term synaptic potentiation / locomotory behavior / insulin-like growth factor receptor binding / ionotropic glutamate receptor binding / Schaffer collateral - CA1 synapse / G-protein beta/gamma-subunit complex binding / adenylate cyclase-activating G protein-coupled receptor signaling pathway / adenylate cyclase-activating dopamine receptor signaling pathway / heterotrimeric G-protein complex / presynaptic membrane / basolateral plasma membrane / postsynaptic density / intracellular signal transduction / apical plasma membrane / axon / GTPase activity / glutamatergic synapse / dendrite / GTP binding / ATP binding / metal ion binding / cytoplasm 類似検索 - 分子機能
ジャーナル: EMBO Rep / 年: 2024 タイトル: Regulatory sites of CaM-sensitive adenylyl cyclase AC8 revealed by cryo-EM and structural proteomics. 著者: Basavraj Khanppnavar / Dina Schuster / Pia Lavriha / Federico Uliana / Merve Özel / Ved Mehta / Alexander Leitner / Paola Picotti / Volodymyr M Korkhov / 要旨: 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 ...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.
タイプ: MAXIMUM LIKELIHOOD / ソフトウェア - 名称: RELION (ver. 3.1.3)
最終 角度割当
タイプ: MAXIMUM LIKELIHOOD
FSC曲線 (解像度の算出)
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原子モデル構築 1
精密化
空間: REAL / プロトコル: RIGID BODY FIT
得られたモデル
PDB-8bv5: Focus refinement of soluble domain of Adenylyl cyclase 8 bound to stimulatory G protein, Forskolin, ATPalphaS, and Ca2+/Calmodulin in lipid nanodisc conditions