ジャーナル: Mol Cell / 年: 2024 タイトル: Multiprotein bridging factor 1 is required for robust activation of the integrated stress response on collided ribosomes. 著者: Kyusik Q Kim / Jeffrey J Li / Ankanahalli N Nanjaraj Urs / Miguel E Pacheco / Victor Lasehinde / Timo Denk / Petr Tesina / Shota Tomomatsu / Yoshitaka Matsuo / Elesa McDonald / Roland ...著者: Kyusik Q Kim / Jeffrey J Li / Ankanahalli N Nanjaraj Urs / Miguel E Pacheco / Victor Lasehinde / Timo Denk / Petr Tesina / Shota Tomomatsu / Yoshitaka Matsuo / Elesa McDonald / Roland Beckmann / Toshifumi Inada / Rachel Green / Hani S Zaher / 要旨: In yeast, multiprotein bridging factor 1 (Mbf1) has been proposed to function in the integrated stress response (ISR) as a transcriptional coactivator by mediating a direct interaction between ...In yeast, multiprotein bridging factor 1 (Mbf1) has been proposed to function in the integrated stress response (ISR) as a transcriptional coactivator by mediating a direct interaction between general transcription machinery and the process's key effector, Gcn4. However, mounting evidence has demonstrated that Mbf1 (and its human homolog EDF1) is recruited to collided ribosomes, a known activator of the ISR. In this study, we connect these otherwise seemingly disparate functions of Mbf1. Our biochemical and structural analyses reveal that Mbf1 functions as a core ISR factor by interacting with collided ribosomes to mediate Gcn2 activation. We further show that Mbf1 serves no role as a transcriptional coactivator of Gcn4. Instead, Mbf1 is required for optimal stress-induced eukaryotic initiation factor 2α (eIF2α) phosphorylation and downstream de-repression of GCN4 translation. Collectively, our data establish that Mbf1 functions in ISR signaling by acting as a direct sensor of stress-induced ribosome collisions.
全体 : glutaraldehyde crosslinked tri- and tetrasome fraction after sucr...
全体
名称: glutaraldehyde crosslinked tri- and tetrasome fraction after sucrose density gradient centrifugation from yeast in vitro translation
要素
複合体: glutaraldehyde crosslinked tri- and tetrasome fraction after sucrose density gradient centrifugation from yeast in vitro translation
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超分子 #1: glutaraldehyde crosslinked tri- and tetrasome fraction after sucr...
超分子
名称: glutaraldehyde crosslinked tri- and tetrasome fraction after sucrose density gradient centrifugation from yeast in vitro translation タイプ: complex / ID: 1 / 親要素: 0
由来(天然)
生物種: Saccharomyces cerevisiae (パン酵母)
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実験情報
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構造解析
手法
クライオ電子顕微鏡法
解析
単粒子再構成法
試料の集合状態
particle
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試料調製
緩衝液
pH: 7.5
凍結
凍結剤: ETHANE
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電子顕微鏡法
顕微鏡
FEI TITAN KRIOS
撮影
フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 平均電子線量: 43.6 e/Å2