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万見- EMDB-10422: Human kinesin-5 motor domain in the AMPPNP state bound to microtubules -
+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-10422 | |||||||||||||||
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タイトル | Human kinesin-5 motor domain in the AMPPNP state bound to microtubules | |||||||||||||||
マップデータ | ||||||||||||||||
試料 |
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キーワード | kinesin / microtubule / mitosis / inhibition / motor / CELL CYCLE | |||||||||||||||
機能・相同性 | 機能・相同性情報 spindle elongation / regulation of mitotic centrosome separation / Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane / Hedgehog 'off' state / Cilium Assembly / Intraflagellar transport / COPI-dependent Golgi-to-ER retrograde traffic / Carboxyterminal post-translational modifications of tubulin / RHOH GTPase cycle / Sealing of the nuclear envelope (NE) by ESCRT-III ...spindle elongation / regulation of mitotic centrosome separation / Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane / Hedgehog 'off' state / Cilium Assembly / Intraflagellar transport / COPI-dependent Golgi-to-ER retrograde traffic / Carboxyterminal post-translational modifications of tubulin / RHOH GTPase cycle / Sealing of the nuclear envelope (NE) by ESCRT-III / Kinesins / PKR-mediated signaling / The role of GTSE1 in G2/M progression after G2 checkpoint / Aggrephagy / Resolution of Sister Chromatid Cohesion / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / Separation of Sister Chromatids / Kinesins / plus-end-directed microtubule motor activity / RHO GTPases activate IQGAPs / RHO GTPases Activate Formins / mitotic centrosome separation / Recruitment of NuMA to mitotic centrosomes / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / MHC class II antigen presentation / COPI-mediated anterograde transport / COPI-dependent Golgi-to-ER retrograde traffic / microtubule motor activity / kinesin complex / spindle organization / microtubule-based movement / mitotic spindle assembly / MHC class II antigen presentation / mitotic spindle organization / 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 / spindle microtubule / structural constituent of cytoskeleton / mitotic spindle / spindle pole / microtubule cytoskeleton organization / spindle / microtubule cytoskeleton / mitotic cell cycle / microtubule binding / microtubule / cell division / GTPase activity / GTP binding / protein kinase binding / protein-containing complex / ATP binding / membrane / nucleus / metal ion binding / cytoplasm / cytosol 類似検索 - 分子機能 | |||||||||||||||
生物種 | Sus scrofa (ブタ) / Homo sapiens (ヒト) | |||||||||||||||
手法 | らせん対称体再構成法 / クライオ電子顕微鏡法 / 解像度: 6.1 Å | |||||||||||||||
データ登録者 | Pena AP / Sweeney A | |||||||||||||||
資金援助 | 英国, 4件
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引用 | ジャーナル: Structure / 年: 2020 タイトル: Structure of Microtubule-Trapped Human Kinesin-5 and Its Mechanism of Inhibition Revealed Using Cryoelectron Microscopy. 著者: Alejandro Peña / Aaron Sweeney / Alexander D Cook / Julia Locke / Maya Topf / Carolyn A Moores / 要旨: Kinesin-5 motors are vital mitotic spindle components, and disruption of their function perturbs cell division. We investigated the molecular mechanism of the human kinesin-5 inhibitor GSK-1, which ...Kinesin-5 motors are vital mitotic spindle components, and disruption of their function perturbs cell division. We investigated the molecular mechanism of the human kinesin-5 inhibitor GSK-1, which allosterically promotes tight microtubule binding. GSK-1 inhibits monomeric human kinesin-5 ATPase and microtubule gliding activities, and promotes the motor's microtubule stabilization activity. Using cryoelectron microscopy, we determined the 3D structure of the microtubule-bound motor-GSK-1 at 3.8 Å overall resolution. The structure reveals that GSK-1 stabilizes the microtubule binding surface of the motor in an ATP-like conformation, while destabilizing regions of the motor around the empty nucleotide binding pocket. Density corresponding to GSK-1 is located between helix-α4 and helix-α6 in the motor domain at its interface with the microtubule. Using a combination of difference mapping and protein-ligand docking, we characterized the kinesin-5-GSK-1 interaction and further validated this binding site using mutagenesis. This work opens up new avenues of investigation of kinesin inhibition and spindle perturbation. | |||||||||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_10422.map.gz | 460.2 KB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-10422-v30.xml emd-10422.xml | 14.9 KB 14.9 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_10422_fsc.xml | 13.9 KB | 表示 | FSCデータファイル |
画像 | emd_10422.png | 159.8 KB | ||
Filedesc metadata | emd-10422.cif.gz | 6.4 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-10422 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-10422 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_10422_validation.pdf.gz | 429.7 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_10422_full_validation.pdf.gz | 429.3 KB | 表示 | |
XML形式データ | emd_10422_validation.xml.gz | 11.2 KB | 表示 | |
CIF形式データ | emd_10422_validation.cif.gz | 15.7 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-10422 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-10422 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_10422.map.gz / 形式: CCP4 / 大きさ: 2.5 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 1.39 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-試料の構成要素
+全体 : AMPPNP bound Human Eg5 motor domain in complex with alpha/beta tubulin
+超分子 #1: AMPPNP bound Human Eg5 motor domain in complex with alpha/beta tubulin
+超分子 #2: AMPPNP bound Human Eg5 motor domain in complex with alpha/beta tubulin
+超分子 #3: AMPPNP bound Human Eg5 motor domain in complex with alpha/beta tubulin
+分子 #1: Tubulin beta chain
+分子 #2: Tubulin alpha-1B chain
+分子 #3: Kinesin-like protein KIF11
+分子 #4: PHOSPHOMETHYLPHOSPHONIC ACID GUANYLATE ESTER
+分子 #5: MAGNESIUM ION
+分子 #6: GUANOSINE-5'-TRIPHOSPHATE
+分子 #7: PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | らせん対称体再構成法 |
試料の集合状態 | filament |
-試料調製
緩衝液 | pH: 7.2 |
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凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI POLARA 300 |
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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: 45.0 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: Tecnai Polara / 画像提供: FEI Company |