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	Allosteric disordering of eIF2B regulates the integrated stress response.
ジャーナル・号・ページ	Nat Chem Biol, Year 2026
掲載日	2026年6月29日
著者	Udit Dalwadi / Advait Subramanian / Aniliese Deal / Julia E Conrad / Tamara Nadjsombati / Meera Venkatesh / Morgane Boone / Pascal F Egea / Lingjie He / Nimit Jain / D John Lee / Yuwei Liu / Lucas C Reineke / Kazuki Saito / Nathaniel Talledge / Hannah Toutkoushian / Maxence Le Vasseur / Francesca Zappa / Raoul J de Groot / Diego Acosta-Alvear / Christopher P Arthur / Jodi Nunnari / Susan Marqusee / Rosalie E Lawrence / Mauro Costa-Mattioli / James J Crawford / Frank J M van Kuppeveld / Tristan I Croll / Peter Walter / Adam Frost /
PubMed 要旨	The ternary complex, composed of eIF2, GTP and initiator methionyl-tRNA, delivers the first amino acid to the ribosome to initiate protein synthesis. Eukaryotic initiation factor 2B (eIF2B) catalyzes ...The ternary complex, composed of eIF2, GTP and initiator methionyl-tRNA, delivers the first amino acid to the ribosome to initiate protein synthesis. Eukaryotic initiation factor 2B (eIF2B) catalyzes GDP to GTP exchange on eIF2, thereby setting the ternary complex level. Stress-induced phosphorylation converts eIF2 from the substrate of eIF2B into an inhibitor (eIF2-P). This conversion reduces ternary complex levels and induces the integrated stress response (ISR). Here we chart an allosteric axis running through eIF2B, revealing the importance of an α-helix in its β-subunit, the 'latch-helix', that hooks onto the α-subunit to induce eIF2B activity. eIF2-P binding promotes latch-helix unhooking, opening eIF2B, which inhibits its activity. Convergently evolved viral proteins stabilize this latch-helix-binding active state of eIF2B. Using these insights, we generated ISR-activating compounds that stabilize eIF2B in its inhibited, unlatched state. Our study thus highlights how long-range eIF2B allostery can be pharmacologically manipulated to sustain or attenuate the ISR.
リンク	Nat Chem Biol / PubMed:42373951
手法	EM (単粒子)
解像度	2.1 - 3.3 Å
構造データ	72462 9y3p EMDB-72462: Eukaryotic translation initiation factor 2-B in its apo form (active-state) (CASP target) PDB-9y3p: Eukaryotic translation initiation factor 2-B in its apo form (active-state) 手法: EM (単粒子) / 解像度: 2.9 Å 72463 9y3q EMDB-72463: Eukaryotic translation initiation factor 2-B in its apo form (inactive-state) (CASP target) PDB-9y3q: Eukaryotic translation initiation factor 2-B in its apo form (inactive-state) 手法: EM (単粒子) / 解像度: 3.3 Å 72466 9y3t EMDB-72466: Eukaryotic translation initiation factor 2-B (eIF2B) with a truncation in the beta subunit (active-like-state) (CASP target) PDB-9y3t: Eukaryotic translation initiation factor 2-B (eIF2B) with a truncation in the beta subunit (active-like-state) 手法: EM (単粒子) / 解像度: 2.5 Å 72467 9y3u EMDB-72467: Eukaryotic translation initiation factor 2-B (eIF2B) with a truncation in the beta subunit (inactive state) (CASP target) PDB-9y3u: Eukaryotic translation initiation factor 2-B (eIF2B) with a truncation in the beta subunit (inactive state) 手法: EM (単粒子) / 解像度: 2.4 Å 72468 9y3v EMDB-72468, PDB-9y3v: Eukaryotic translation initiation factor 2-B (eIF2B) bound to the viral effector AcP10 手法: EM (単粒子) / 解像度: 2.9 Å 72477 9y4b EMDB-72477: Eukaryotic translation initiation factor 2-B (eIF2B) with a truncation in the beta subunit (active-like-state) bound to the viral effector AcP10 (CASP target) PDB-9y4b: Eukaryotic translation initiation factor 2-B (eIF2B) with a truncation in the beta subunit (active-like-state) bound to the viral effector AcP10 手法: EM (単粒子) / 解像度: 2.1 Å 72499 9y4w EMDB-72499: Eukaryotic translation initiation factor 2-B (eIF2B) with a truncation in the beta subunit (active-like-state) asymmetrically bound to the viral effector AcP10 (CASP target) PDB-9y4w: Eukaryotic translation initiation factor 2-B (eIF2B) with a truncation in the beta subunit (active-like-state) asymmetrically bound to the viral effector AcP10 手法: EM (単粒子) / 解像度: 2.4 Å 72520 9y5r EMDB-72520, PDB-9y5r: Eukaryotic translation initiation factor 2-B (eIF2B) bound to phosphorylated eIF2alpha (NTD) 手法: EM (単粒子) / 解像度: 3.01 Å 72521 9y5s EMDB-72521, PDB-9y5s: eIF2B lacking the latch helix bound to ISRACT-01 (Inactive state) 手法: EM (単粒子) / 解像度: 3.1 Å 72522 9y5t EMDB-72522, PDB-9y5t: eIF2B lacking the latch helix bound to ISRACT-02 (Active state) 手法: EM (単粒子) / 解像度: 2.78 Å 72523 9y5u EMDB-72523, PDB-9y5u: eIF2B lacking the latch helix bound to ISRACT-02 (Inactive state) 手法: EM (単粒子) / 解像度: 2.9 Å
化合物	ChemComp-CL: Unknown entry ChemComp-IMD: IMIDAZOLE ChemComp-ZN: Unknown entry ChemComp-PO4: PHOSPHATE ION ChemComp-MG: Unknown entry ChemComp-HOH: WATER PDB-1css: ALPHA-FLUORO ACID AND ALPHA-FLUORO AMIDE ANALOGS OF ACETYL-COA AS INHIBITORS OF OF CITRATE SYNTHASE: EFFECT OF PKA MATCHING ON BINDING AFFINITY AND HYDROGEN BOND LENGTH PDB-1csr: Alpha-fluoro acid and alpha-fluoro amide analogs of acetyl-coa as inhibitors of of citrate synthase: effect of pka matching on binding affinity and hydrogen bond length
由来	homo sapiens (ヒト) beluga whale coronavirus sw1 (ウイルス)
キーワード	TRANSLATION / Guanine nucleotide exchange factor / GEF / initiation