登録情報 データベース : PDB / ID : 7b1g 構造の表示 ダウンロードとリンクタイトル TRPC4 in complex with Calmodulin 要素Calmodulin-1 Transient receptor potential cation channel subfamily c member 4a 詳細キーワード TRANSPORT PROTEIN / ION CHANNEL / TRPC4 / COMPLEX / MEMBRANE PROTEIN / CALMODULIN機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
CaMK IV-mediated phosphorylation of CREB / Cam-PDE 1 activation / CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde / Glycogen breakdown (glycogenolysis) / Activation of RAC1 downstream of NMDARs / Reduction of cytosolic Ca++ levels / Sodium/Calcium exchangers / Activation of Ca-permeable Kainate Receptor / CLEC7A (Dectin-1) induces NFAT activation / Synthesis of IP3 and IP4 in the cytosol ... CaMK IV-mediated phosphorylation of CREB / Cam-PDE 1 activation / CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde / Glycogen breakdown (glycogenolysis) / Activation of RAC1 downstream of NMDARs / Reduction of cytosolic Ca++ levels / Sodium/Calcium exchangers / Activation of Ca-permeable Kainate Receptor / CLEC7A (Dectin-1) induces NFAT activation / Synthesis of IP3 and IP4 in the cytosol / RHO GTPases activate PAKs / Calmodulin induced events / Inactivation, recovery and regulation of the phototransduction cascade / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / Calcineurin activates NFAT / eNOS activation / Ion transport by P-type ATPases / Unblocking of NMDA receptors, glutamate binding and activation / Protein methylation / RAF activation / VEGFR2 mediated vascular permeability / RAS processing / Smooth Muscle Contraction / Ca2+ pathway / FCERI mediated Ca+2 mobilization / RHO GTPases activate IQGAPs / Extra-nuclear estrogen signaling / RAF/MAP kinase cascade / store-operated calcium channel activity / PKA activation / Platelet degranulation / cation channel complex / Stimuli-sensing channels / Ion homeostasis / type 3 metabotropic glutamate receptor binding / inositol 1,4,5 trisphosphate binding / organelle localization by membrane tethering / regulation of cardiac muscle cell action potential / mitochondrion-endoplasmic reticulum membrane tethering / autophagosome membrane docking / nitric-oxide synthase binding / monoatomic cation transport / protein phosphatase activator activity / adenylate cyclase binding / catalytic complex / detection of calcium ion / regulation of cardiac muscle contraction / negative regulation of ryanodine-sensitive calcium-release channel activity / calcium channel inhibitor activity / cellular response to interferon-beta / monoatomic cation channel activity / phosphatidylinositol 3-kinase binding / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / positive regulation of protein dephosphorylation / regulation of ryanodine-sensitive calcium-release channel activity / titin binding / voltage-gated potassium channel complex / sperm midpiece / calcium channel complex / regulation of cytosolic calcium ion concentration / adenylate cyclase activator activity / nitric-oxide synthase regulator activity / regulation of heart rate / sarcomere / protein serine/threonine kinase activator activity / regulation of cytokinesis / calcium ion transmembrane transport / positive regulation of receptor signaling pathway via JAK-STAT / spindle microtubule / cellular response to type II interferon / spindle pole / G2/M transition of mitotic cell cycle / calcium-dependent protein binding / myelin sheath / growth cone / transmembrane transporter binding / protein domain specific binding / centrosome / calcium ion binding / protein kinase binding / nucleoplasm / plasma membrane / cytoplasm / cytosol 類似検索 - 分子機能 Transient receptor ion channel II / Transient receptor ion channel domain / Transient receptor ion channel II / Transient receptor potential channel, canonical / Ankyrin repeat / EF-hand domain pair / Ankyrin repeats (3 copies) / Ankyrin repeat profile. / ankyrin repeats / Ankyrin repeat ... Transient receptor ion channel II / Transient receptor ion channel domain / Transient receptor ion channel II / Transient receptor potential channel, canonical / Ankyrin repeat / EF-hand domain pair / Ankyrin repeats (3 copies) / Ankyrin repeat profile. / ankyrin repeats / Ankyrin repeat / Ankyrin repeat-containing domain superfamily / EF-hand, calcium binding motif / EF-Hand 1, calcium-binding site / EF-hand calcium-binding domain. / EF-hand calcium-binding domain profile. / EF-hand domain / Ion transport domain / Ion transport protein / EF-hand domain pair 類似検索 - ドメイン・相同性 (2R)-3-(phosphonooxy)propane-1,2-diyl dihexanoate / Calmodulin-1 / Transient receptor potential cation channel subfamily c member 4a 類似検索 - 構成要素生物種 Danio rerio (ゼブラフィッシュ)Mus musculus (ハツカネズミ)手法 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.6 Å 詳細データ登録者 Vinayagam, D. / Quentin, D. / Sistel, O. / Merino, F. / Stabrin, M. / Hofnagel, O. / Ledeboer, M.W. / Malojcic, G. / Raunser, S. 資金援助 ドイツ, 1件 詳細 詳細を隠す組織 認可番号 国 Max Planck Society ドイツ
引用ジャーナル : Elife / 年 : 2020タイトル : Structural basis of TRPC4 regulation by calmodulin and pharmacological agents.著者: Deivanayagabarathy Vinayagam / Dennis Quentin / Jing Yu-Strzelczyk / Oleg Sitsel / Felipe Merino / Markus Stabrin / Oliver Hofnagel / Maolin Yu / Mark W Ledeboer / Georg Nagel / Goran ... 著者 : Deivanayagabarathy Vinayagam / Dennis Quentin / Jing Yu-Strzelczyk / Oleg Sitsel / Felipe Merino / Markus Stabrin / Oliver Hofnagel / Maolin Yu / Mark W Ledeboer / Georg Nagel / Goran Malojcic / Stefan Raunser / 要旨 : Canonical transient receptor potential channels (TRPC) are involved in receptor-operated and/or store-operated Ca signaling. Inhibition of TRPCs by small molecules was shown to be promising in ... Canonical transient receptor potential channels (TRPC) are involved in receptor-operated and/or store-operated Ca signaling. Inhibition of TRPCs by small molecules was shown to be promising in treating renal diseases. In cells, the channels are regulated by calmodulin (CaM). Molecular details of both CaM and drug binding have remained elusive so far. Here, we report structures of TRPC4 in complex with three pyridazinone-based inhibitors and CaM. The structures reveal that all the inhibitors bind to the same cavity of the voltage-sensing-like domain and allow us to describe how structural changes from the ligand-binding site can be transmitted to the central ion-conducting pore of TRPC4. CaM binds to the rib helix of TRPC4, which results in the ordering of a previously disordered region, fixing the channel in its closed conformation. This represents a novel CaM-induced regulatory mechanism of canonical TRP channels. 履歴 登録 2020年11月24日 登録サイト : PDBE / 処理サイト : PDBE改定 1.0 2020年12月9日 Provider : repository / タイプ : Initial release改定 1.1 2024年5月1日 Group : Data collection / Database references / Refinement descriptionカテゴリ : chem_comp_atom / chem_comp_bond ... chem_comp_atom / chem_comp_bond / database_2 / em_3d_fitting_list / pdbx_initial_refinement_model Item : _database_2.pdbx_DOI / _database_2.pdbx_database_accession ... _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _em_3d_fitting_list.accession_code / _em_3d_fitting_list.initial_refinement_model_id / _em_3d_fitting_list.source_name / _em_3d_fitting_list.type
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