登録情報 データベース : PDB / ID : 6tiw 構造の表示 ダウンロードとリンクタイトル Human kinesin-5 motor domain in the GSK state bound to microtubules (Conformation 2) 要素Kinesin-like protein KIF11 Tubulin alpha-1B chain Tubulin beta chain 詳細キーワード CELL CYCLE / kinesin / microtubule / mitosis / inhibition / motor機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
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 / mitotic centrosome separation / RHO GTPases Activate Formins / 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 Kinesin-associated microtubule-binding domain / Kinesin-associated microtubule-binding / : / : / Kinesin motor domain / Kinesin / Helix hairpin bin / Tubulin/FtsZ, C-terminal domain / Tubulin/FtsZ, GTPase domain / Kinesin motor domain signature. ... Kinesin-associated microtubule-binding domain / Kinesin-associated microtubule-binding / : / : / Kinesin motor domain / Kinesin / Helix hairpin bin / Tubulin/FtsZ, C-terminal domain / Tubulin/FtsZ, GTPase domain / Kinesin motor domain signature. / Kinesin motor domain, conserved site / Kinesin motor domain / Kinesin motor domain profile. / Kinesin motor, catalytic domain. ATPase. / Kinesin motor domain / 60s Ribosomal Protein L30; Chain: A; / Kinesin motor domain superfamily / Alpha tubulin / Tubulin-beta mRNA autoregulation signal. / Beta tubulin, autoregulation binding site / Beta tubulin / Tubulin / Tubulin, C-terminal / Tubulin C-terminal domain / Tubulin, conserved site / Tubulin subunits alpha, beta, and gamma signature. / Tubulin/FtsZ family, C-terminal domain / Tubulin/FtsZ-like, C-terminal domain / Tubulin/FtsZ, C-terminal / Tubulin/FtsZ, 2-layer sandwich domain / Tubulin/FtsZ family, GTPase domain / Tubulin/FtsZ family, GTPase domain / Tubulin/FtsZ, GTPase domain / Tubulin/FtsZ, GTPase domain superfamily / Helix Hairpins / P-loop containing nucleoside triphosphate hydrolase / Rossmann fold / 2-Layer Sandwich / Orthogonal Bundle / 3-Layer(aba) Sandwich / Mainly Alpha / Alpha Beta 類似検索 - ドメイン・相同性 PHOSPHOMETHYLPHOSPHONIC ACID GUANYLATE ESTER / Chem-MZK / Tubulin beta chain / Kinesin-like protein KIF11 / Tubulin alpha-1B chain 類似検索 - 構成要素生物種 Homo sapiens (ヒト)Sus scrofa (ブタ)手法 電子顕微鏡法 / らせん対称体再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.8 Å 詳細データ登録者 Pena, A. / Sweeney, A. / Cook, A.D. / Moores, C.A. / Topf, M. 資金援助 英国, 3件 詳細 詳細を隠す組織 認可番号 国 Wellcome Trust 202679/Z/16/Z and 206166/Z/17/Z 英国 Medical Research Council (United Kingdom) MR/J003867/1 英国 Medical Research Council (United Kingdom) MR/N013867/1 英国
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. 残り1件を表示 表示を減らす履歴 登録 2019年11月22日 登録サイト : PDBE / 処理サイト : PDBE改定 1.0 2020年3月4日 Provider : repository / タイプ : Initial release改定 1.1 2020年4月15日 Group : Database references / カテゴリ : citationItem : _citation.journal_volume / _citation.page_first / _citation.page_last改定 1.2 2020年7月8日 Group : Data processing / カテゴリ : em_3d_reconstructionItem : _em_3d_reconstruction.resolution / _em_3d_reconstruction.resolution_method改定 1.3 2024年5月15日 Group : Data collection / Database references / Derived calculationsカテゴリ : chem_comp_atom / chem_comp_bond ... chem_comp_atom / chem_comp_bond / database_2 / pdbx_struct_conn_angle / struct_conn Item : _database_2.pdbx_DOI / _database_2.pdbx_database_accession ... _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_conn_angle.ptnr1_auth_asym_id / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr2_auth_asym_id / _pdbx_struct_conn_angle.ptnr2_label_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_asym_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_label_asym_id
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