EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	The role of the troponin T interactions with actin in regulation of cardiac thin filament revealed by the troponin T pathogenic variant Ile79Asn.
ジャーナル・号・ページ	J Mol Cell Cardiol, Vol. 204, Page 55-67, Year 2025
掲載日	2025年5月22日
著者	Cristina M Risi / Maicon Landim-Vieira / Betty Belknap / P Bryant Chase / Jose R Pinto / Vitold E Galkin /
PubMed 要旨	Cardiac muscle contraction/relaxation cycle depends on the rising and falling Ca levels in sarcomeres that control the extent of interactions between myosin-based thick and actin-based thin filaments. ...Cardiac muscle contraction/relaxation cycle depends on the rising and falling Ca levels in sarcomeres that control the extent of interactions between myosin-based thick and actin-based thin filaments. Cardiac thin filament (cTF) consists of actin, tropomyosin (Tm) that regulates myosin binding to actin, and troponin complex that governs Tm position upon Ca-binding. Troponin has three subunits - Ca-binding troponin C (TnC), Tm stabilizing troponin T (TnT), and inhibitory troponin I (TnI). TnT N-terminus (TnT1) interactions with actin stabilize the inhibited state of cTF. TnC, TnI, and Tm work in concert to control actomyosin interactions. Cryo-electron microscopy (cryo-EM) provided factual structures of healthy cTF, but structures of cTF carrying missense mutations linked to human cardiomyopathy are unknown. Variant Ile79Asn in human cardiac TnT (TnT-I79N) increases myofilament Ca sensitivity and slows cross-bridge kinetics, leading to severe hypertrophic/restrictive cardiomyopathy. Here, we used TnT-I79N mutation as a tool to examine the role of TnT1 in the complex mechanism of cTF regulation. Comparison of the cryo-EM structures of murine wild type and TnT-I79N native cTFs at systolic Ca levels (pCa = 5.8) demonstrates that TnT-I79N causes 1) dissociation of the TnT1 loop from its actin interface that results in Tm release to a more activated position, 2) reduced interaction of TnI C-terminus with actin-Tm, and 3) increased frequency of Ca-bound regulatory units. Our data indicate that the TnT1 loop is a crucial element of the allosteric regulatory network that couples Tn subunits and Tm to maintain adequate cTF response to physiological Ca levels during a heartbeat.
リンク	J Mol Cell Cardiol / PubMed:40412797 / PubMed Central
手法	EM (単粒子)
解像度	4.0 - 5.7 Å
構造データ	47449 9e2e EMDB-47449, PDB-9e2e: The structure of the junction region of the wild-type murine native cardiac thin filament in Ca2+-free state 手法: EM (単粒子) / 解像度: 4.0 Å 48447 9mo4 EMDB-48447, PDB-9mo4: Structure of native murine cardiac thin filament at pCa=5.8 in Ca2+-free state (lower strand) 手法: EM (単粒子) / 解像度: 5.3 Å 48448 9mo5 EMDB-48448, PDB-9mo5: Structure of native murine cardiac thin filament at pCa=5.8 in Ca2+-bound partially activated state (lower strand) 手法: EM (単粒子) / 解像度: 5.3 Å 48449 9mo6 EMDB-48449, PDB-9mo6: Structure of native murine cardiac thin filament at pCa=5.8 in Ca2+-free tilted state (lower strand) 手法: EM (単粒子) / 解像度: 5.3 Å 48450 9mo7 EMDB-48450, PDB-9mo7: Structure of native murine cardiac thin filament at pCa=5.8 in Ca2+-bound fully activated state (lower strand) 手法: EM (単粒子) / 解像度: 5.2 Å 48451 9mo8 EMDB-48451, PDB-9mo8: Structure of native murine cardiac thin filament at pCa=5.8 in Ca2+-free state (upper strand) 手法: EM (単粒子) / 解像度: 5.2 Å 48452 9mo9 EMDB-48452, PDB-9mo9: Structure of native murine cardiac thin filament variant I79N in troponin T at pCa=5.8 in Ca2+-free rotated state (lower strand) 手法: EM (単粒子) / 解像度: 5.6 Å 48453 9moa EMDB-48453, PDB-9moa: Structure of native murine cardiac thin filament variant I79N in troponin T at pCa=5.8 in Ca2+-free tilted state (lower strand) 手法: EM (単粒子) / 解像度: 5.4 Å 48454 9mob EMDB-48454, PDB-9mob: Structure of native murine cardiac thin filament variant I79N in troponin T at pCa=5.8 in Ca2+-free state (upper strand) 手法: EM (単粒子) / 解像度: 5.5 Å 48455 9moc EMDB-48455, PDB-9moc: Structure of native murine cardiac thin filament variant I79N in troponin T at pCa=5.8 in Ca2+-free rotated state (upper strand) 手法: EM (単粒子) / 解像度: 5.6 Å 48456 9mod EMDB-48456, PDB-9mod: Structure of native murine cardiac thin filament variant I79N in troponin T at pCa=5.8 in Ca2+-free tilted state (upper strand) 手法: EM (単粒子) / 解像度: 5.7 Å 48467 9moi EMDB-48467, PDB-9moi: Structure of native murine cardiac thin filament at pCa=5.8 in Ca2+-free rotated state (lower strand) 手法: EM (単粒子) / 解像度: 5.4 Å 48468 9mok EMDB-48468, PDB-9mok: Structure of native murine cardiac thin filament at pCa=5.8 in Ca2+-free rotated state (upper strand) 手法: EM (単粒子) / 解像度: 5.6 Å 48469 9mol EMDB-48469, PDB-9mol: Structure of native murine cardiac thin filament at pCa=5.8 in Ca2+-free tilted state (upper strand) 手法: EM (単粒子) / 解像度: 5.2 Å 48470 9mom EMDB-48470, PDB-9mom: Structure of native murine cardiac thin filament at pCa=5.8 in Ca2+-bound partially activated state (upper strand) 手法: EM (単粒子) / 解像度: 5.1 Å 48471 9mon EMDB-48471, PDB-9mon: Structure of native murine cardiac thin filament at pCa=5.8 in Ca2+-bound fully activated state (upper strand) 手法: EM (単粒子) / 解像度: 5.2 Å 48476 9moo EMDB-48476, PDB-9moo: Structure of native murine cardiac thin filament variant I79N in troponin T at pCa=5.8 in Ca2+-free state (lower strand) 手法: EM (単粒子) / 解像度: 5.2 Å 48477 9mop EMDB-48477, PDB-9mop: Structure of native murine cardiac thin filament variant I79N in troponin T at pCa=5.8 in Ca2+-bound fully activated state (lower strand) 手法: EM (単粒子) / 解像度: 5.0 Å 48482 9mou EMDB-48482, PDB-9mou: Structure of native murine cardiac thin filament variant I79N in troponin T at pCa=5.8 in Ca2+-bound partially activated state (upper strand) 手法: EM (単粒子) / 解像度: 5.6 Å 48483 9mow EMDB-48483, PDB-9mow: Structure of native murine cardiac thin filament variant I79N in troponin T at pCa=5.8 in Ca2+-bound fully activated state (upper strand) 手法: EM (単粒子) / 解像度: 4.9 Å 48484 9mox EMDB-48484, PDB-9mox: Structure of native murine cardiac thin filament variant I79N in troponin T at pCa=5.8 in Ca2+-bound partially activated state (lower strand) 手法: EM (単粒子) / 解像度: 5.2 Å
化合物	ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP / ADP, エネルギー貯蔵分子YM ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-CA*: Unknown entry / カルシウムジカチオン
由来	mus musculus (ハツカネズミ)
キーワード	MOTOR PROTEIN / thin filament / troponin T / muscle / cryo-EM / troponin / tropomyosin / muscle structure