- EMDB-20134: Structure of a drug-like molecule stalled PCSK9 ribosome nascent ... -
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基本情報
登録情報
データベース: EMDB / ID: EMD-20134
タイトル
Structure of a drug-like molecule stalled PCSK9 ribosome nascent chain complex (PCSK9-RNC) with AP tRNA and PE tRNA (sample prepared with a short incubation time)
マップデータ
Structure of a drug-like molecule stalled PCSK9 ribosome nascent chain complex (PCSK9-RNC) with AP tRNA and PE tRNA (sample prepared with a short incubation time)
試料
複合体: Structure of a drug-like molecule stalled PCSK9 ribosome nascent chain complex (PCSK9-RNC) with AP tRNA and PE tRNA (sample prepared with a short incubation time)
National Institutes of Health/National Human Genome Research Institute
R01-GM065050
米国
引用
ジャーナル: Nat Struct Mol Biol / 年: 2019 タイトル: Structural basis for selective stalling of human ribosome nascent chain complexes by a drug-like molecule. 著者: Wenfei Li / Fred R Ward / Kim F McClure / Stacey Tsai-Lan Chang / Elizabeth Montabana / Spiros Liras / Robert G Dullea / Jamie H D Cate / 要旨: The drug-like molecule PF-06446846 (PF846) binds the human ribosome and selectively blocks the translation of a small number of proteins by an unknown mechanism. In structures of PF846-stalled human ...The drug-like molecule PF-06446846 (PF846) binds the human ribosome and selectively blocks the translation of a small number of proteins by an unknown mechanism. In structures of PF846-stalled human ribosome nascent chain complexes, PF846 binds in the ribosome exit tunnel in a eukaryotic-specific pocket formed by 28S ribosomal RNA, and alters the path of the nascent polypeptide chain. PF846 arrests the translating ribosome in the rotated state of translocation, in which the peptidyl-transfer RNA 3'-CCA end is improperly docked in the peptidyl transferase center. Selections of messenger RNAs from mRNA libraries using translation extracts reveal that PF846 can stall translation elongation, arrest termination or even enhance translation, depending on nascent chain sequence context. These results illuminate how a small molecule selectively targets translation by the human ribosome, and provides a foundation for developing small molecules that modulate the production of proteins of therapeutic interest.
ダウンロード / ファイル: emd_20134.map.gz / 形式: CCP4 / 大きさ: 421.9 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
注釈
Structure of a drug-like molecule stalled PCSK9 ribosome nascent chain complex (PCSK9-RNC) with AP tRNA and PE tRNA (sample prepared with a short incubation time)
全体 : Structure of a drug-like molecule stalled PCSK9 ribosome nascent ...
全体
名称: Structure of a drug-like molecule stalled PCSK9 ribosome nascent chain complex (PCSK9-RNC) with AP tRNA and PE tRNA (sample prepared with a short incubation time)
要素
複合体: Structure of a drug-like molecule stalled PCSK9 ribosome nascent chain complex (PCSK9-RNC) with AP tRNA and PE tRNA (sample prepared with a short incubation time)
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超分子 #1: Structure of a drug-like molecule stalled PCSK9 ribosome nascent ...
超分子
名称: Structure of a drug-like molecule stalled PCSK9 ribosome nascent chain complex (PCSK9-RNC) with AP tRNA and PE tRNA (sample prepared with a short incubation time) タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1
由来(天然)
生物種: Homo sapiens (ヒト)
組換発現
生物種: Homo sapiens (ヒト) / 組換細胞: HeLa
分子量
理論値: 4.3 MDa
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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
グリッド
詳細: unspecified
凍結
凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 4 K
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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: 50.0 e/Å2
電子線
加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN
電子光学系
照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD
実験機器
モデル: Titan Krios / 画像提供: FEI Company
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画像解析
最終 再構成
解像度のタイプ: BY AUTHOR / 解像度: 4.7 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 8433