登録情報 データベース : PDB / ID : 8dyu 構造の表示 ダウンロードとリンクタイトル Structure of human cytoplasmic dynein-1 bound to two Lis1 proteins 要素Cytoplasmic dynein 1 heavy chain 1 Platelet-activating factor acetylhydrolase IB subunit beta 詳細キーワード MOTOR PROTEIN (モータータンパク質) / dynein (ダイニン) / transport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
corpus callosum morphogenesis / establishment of planar polarity of embryonic epithelium / microtubule cytoskeleton organization involved in establishment of planar polarity / ameboidal-type cell migration / interneuron migration / 1-alkyl-2-acetylglycerophosphocholine esterase complex / maintenance of centrosome location / microtubule sliding / platelet activating factor metabolic process / acrosome assembly ... corpus callosum morphogenesis / establishment of planar polarity of embryonic epithelium / microtubule cytoskeleton organization involved in establishment of planar polarity / ameboidal-type cell migration / interneuron migration / 1-alkyl-2-acetylglycerophosphocholine esterase complex / maintenance of centrosome location / microtubule sliding / platelet activating factor metabolic process / acrosome assembly / radial glia-guided pyramidal neuron migration / microtubule organizing center organization / cerebral cortex neuron differentiation / positive regulation of intracellular transport / central region of growth cone / positive regulation of embryonic development / reelin-mediated signaling pathway / regulation of metaphase plate congression / establishment of centrosome localization / positive regulation of cytokine-mediated signaling pathway / cortical microtubule organization / establishment of spindle localization / astral microtubule / positive regulation of spindle assembly / layer formation in cerebral cortex / nuclear membrane disassembly / auditory receptor cell development / positive regulation of dendritic spine morphogenesis / vesicle transport along microtubule / stem cell division / stereocilium / myeloid leukocyte migration / P-body assembly / dynein complex / COPI-independent Golgi-to-ER retrograde traffic / microtubule plus-end binding / minus-end-directed microtubule motor activity / cytoplasmic dynein complex / retrograde axonal transport / negative regulation of JNK cascade / dynein light intermediate chain binding / brain morphogenesis / 繊毛 / nuclear migration / osteoclast development / microtubule associated complex / kinesin complex / dynein intermediate chain binding / dynein complex binding / cochlea development / transmission of nerve impulse / cell leading edge / germ cell development / dynactin binding / establishment of mitotic spindle orientation / phospholipase binding / neuromuscular process controlling balance / neuroblast proliferation / protein secretion / positive regulation of axon extension / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / cytoplasmic microtubule / microtubule-based process / COPI-mediated anterograde transport / lipid catabolic process / regulation of microtubule cytoskeleton organization / cytoplasmic microtubule organization / stress granule assembly / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / regulation of mitotic spindle organization / axon cytoplasm / JNK cascade / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / Recruitment of mitotic centrosome proteins and complexes / Resolution of Sister Chromatid Cohesion / Recruitment of NuMA to mitotic centrosomes / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / Anchoring of the basal body to the plasma membrane / MHC class II antigen presentation / positive regulation of mitotic cell cycle / adult locomotory behavior / AURKA Activation by TPX2 / mitotic spindle organization / filopodium / RHO GTPases Activate Formins / hippocampus development / phosphoprotein binding / neuron migration / modulation of chemical synaptic transmission / Schaffer collateral - CA1 synapse / 動原体 / microtubule cytoskeleton organization / cerebral cortex development / Aggrephagy / HCMV Early Events / Separation of Sister Chromatids / azurophil granule lumen / Regulation of PLK1 Activity at G2/M Transition 類似検索 - 分子機能 Dynein regulator LIS1 / LIS1, N-terminal / LisH / Dynein heavy chain, AAA 5 extension domain / Dynein heavy chain AAA lid domain / Lissencephaly type-1-like homology motif / Dynein heavy chain, C-terminal domain / Dynein heavy chain, C-terminal domain, barrel region / Dynein heavy chain C-terminal domain / P-loop containing dynein motor region ... Dynein regulator LIS1 / LIS1, N-terminal / LisH / Dynein heavy chain, AAA 5 extension domain / Dynein heavy chain AAA lid domain / Lissencephaly type-1-like homology motif / Dynein heavy chain, C-terminal domain / Dynein heavy chain, C-terminal domain, barrel region / Dynein heavy chain C-terminal domain / P-loop containing dynein motor region / Dynein heavy chain, tail / Dynein heavy chain, N-terminal region 1 / Dynein heavy chain / Dynein heavy chain region D6 P-loop domain / Dynein heavy chain, linker / Dynein heavy chain, AAA module D4 / Dynein heavy chain, coiled coil stalk / Dynein heavy chain, hydrolytic ATP-binding dynein motor region / Dynein heavy chain, ATP-binding dynein motor region / Dynein heavy chain AAA lid domain / Dynein heavy chain AAA lid domain superfamily / Dynein heavy chain, domain 2, N-terminal / Dynein heavy chain, linker, subdomain 3 / Dynein heavy chain, AAA1 domain, small subdomain / Dynein heavy chain region D6 P-loop domain / Dynein heavy chain, N-terminal region 2 / Hydrolytic ATP binding site of dynein motor region / Microtubule-binding stalk of dynein motor / P-loop containing dynein motor region D4 / ATP-binding dynein motor region / Dynein heavy chain AAA lid domain / LIS1 homology (LisH) motif profile. / LIS1 homology motif / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / WD domain, G-beta repeat / WD40リピート / WD40リピート / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性 ADENOSINE-5'-DIPHOSPHATE / ADENOSINE-5'-TRIPHOSPHATE / Platelet-activating factor acetylhydrolase IB subunit beta / Cytoplasmic dynein 1 heavy chain 1 類似検索 - 構成要素生物種 Homo sapiens (ヒト)手法 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 4 Å 詳細データ登録者 Reimer, J.M. / DeSantis, M. / Reck-Peterson, S.L. / Leschziner, A.E. 資金援助 米国, 2件 詳細 詳細を隠す組織 認可番号 国 Damon Runyon Cancer Research Foundation DRG-2370-19 米国 National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) R01 GM107214 米国
引用ジャーナル : Elife / 年 : 2023タイトル : Structures of human dynein in complex with the lissencephaly 1 protein, LIS1.
著者 :
Janice M Reimer / Morgan E DeSantis / Samara L Reck-Peterson / Andres E Leschziner / 要旨 :
The lissencephaly 1 protein, LIS1, is mutated in type-1 lissencephaly and is a key regulator of cytoplasmic dynein-1. At a molecular level, current models propose that LIS1 activates dynein by ... The lissencephaly 1 protein, LIS1, is mutated in type-1 lissencephaly and is a key regulator of cytoplasmic dynein-1. At a molecular level, current models propose that LIS1 activates dynein by relieving its autoinhibited form. Previously we reported a 3.1 Å structure of yeast dynein bound to Pac1, the yeast homologue of LIS1, which revealed the details of their interactions (Gillies et al., 2022). Based on this structure, we made mutations that disrupted these interactions and showed that they were required for dynein's function in vivo in yeast. We also used our yeast dynein-Pac1 structure to design mutations in human dynein to probe the role of LIS1 in promoting the assembly of active dynein complexes. These mutations had relatively mild effects on dynein activation, suggesting that there may be differences in how dynein and Pac1/LIS1 interact between yeast and humans. Here, we report cryo-EM structures of human dynein-LIS1 complexes. Our new structures reveal the differences between the yeast and human systems, provide a blueprint to disrupt the human dynein-LIS1 interactions more accurately, and map type-1 lissencephaly disease mutations, as well as mutations in dynein linked to malformations of cortical development/intellectual disability, in the context of the dynein-LIS1 complex. 残り1件を表示 表示を減らす履歴 登録 2022年8月5日 登録サイト : RCSB / 処理サイト : RCSB改定 1.0 2023年2月1日 Provider : repository / タイプ : Initial release