登録情報 データベース : EMDB / ID : EMD-19132 ダウンロードとリンクタイトル Structure of dynein-2 intermediate chain DYNC2I2 (WDR34) in complex with dynein-2 heavy chain DYNC2H1. マップデータLocally refined map, locally sharpened with locscale 詳細 試料複合体 : Dynein-2 complexタンパク質・ペプチド : Methylated-DNA--protein-cysteine methyltransferase,Cytoplasmic dynein 2 heavy chain 1タンパク質・ペプチド : Cytoplasmic dynein 2 intermediate chain 1タンパク質・ペプチド : Cytoplasmic dynein 2 intermediate chain 2タンパク質・ペプチド : Dynein light chain roadblock-type 1タンパク質・ペプチド : Dynein light chain 1, cytoplasmic 詳細 キーワード dynein / cilia / intraflagellar transport / complex / TRANSPORT PROTEIN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
MGMT-mediated DNA damage reversal / nitric-oxide synthase inhibitor activity / deoxyribonuclease inhibitor activity / negative regulation of DNA strand resection involved in replication fork processing / visual behavior / intraciliary retrograde transport / methylated-DNA-[protein]-cysteine S-methyltransferase / methylated-DNA-[protein]-cysteine S-methyltransferase activity / cilium movement involved in cell motility / 9+2 motile cilium ... MGMT-mediated DNA damage reversal / nitric-oxide synthase inhibitor activity / deoxyribonuclease inhibitor activity / negative regulation of DNA strand resection involved in replication fork processing / visual behavior / intraciliary retrograde transport / methylated-DNA-[protein]-cysteine S-methyltransferase / methylated-DNA-[protein]-cysteine S-methyltransferase activity / cilium movement involved in cell motility / 9+2 motile cilium / intraciliary transport / dynein light chain binding / spinal cord motor neuron differentiation / motile cilium assembly / dynein heavy chain binding / DNA-methyltransferase activity / Activation of BIM and translocation to mitochondria / embryonic skeletal system morphogenesis / ciliary tip / Intraflagellar transport / negative regulation of nitric oxide biosynthetic process / dynein complex / DNA ligation / negative regulation of phosphorylation / COPI-independent Golgi-to-ER retrograde traffic / coronary vasculature development / minus-end-directed microtubule motor activity / non-motile cilium assembly / DNA alkylation repair / dynein light intermediate chain binding / protein localization to cilium / cytoplasmic dynein complex / positive regulation of smoothened signaling pathway / ciliary plasm / dorsal/ventral pattern formation / enzyme inhibitor activity / determination of left/right symmetry / embryonic limb morphogenesis / positive regulation of double-strand break repair / microtubule motor activity / ciliary base / dynein intermediate chain binding / Macroautophagy / pericentriolar material / microtubule-based movement / Golgi organization / cytoskeletal motor activity / axoneme / positive regulation of insulin secretion involved in cellular response to glucose stimulus / tertiary granule membrane / ficolin-1-rich granule membrane / spermatid development / cilium assembly / Hedgehog 'off' state / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / COPI-mediated anterograde transport / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / forebrain development / Recruitment of mitotic centrosome proteins and complexes / axon cytoplasm / Recruitment of NuMA to mitotic centrosomes / Anchoring of the basal body to the plasma membrane / Resolution of Sister Chromatid Cohesion / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / substantia nigra development / MHC class II antigen presentation / centriole / AURKA Activation by TPX2 / ciliary basal body / filopodium / kidney development / methyltransferase activity / RHO GTPases Activate Formins / HCMV Early Events / cilium / protein processing / mitotic spindle / kinetochore / Aggrephagy / Separation of Sister Chromatids / Regulation of PLK1 Activity at G2/M Transition / apical part of cell / site of double-strand break / scaffold protein binding / methylation / microtubule / cytoskeleton / DNA repair / centrosome / DNA damage response / Neutrophil degranulation / negative regulation of apoptotic process / protein-containing complex binding / apoptotic process / enzyme binding / Golgi apparatus / ATP hydrolysis activity 類似検索 - 分子機能 Cytoplasmic dynein 2 intermediate chain 1 / : / Cytoplasmic dynein 2 heavy chain 1, AAA+ ATPase domain / Methylguanine DNA methyltransferase, ribonuclease-like domain / 6-O-methylguanine DNA methyltransferase, ribonuclease-like domain / Dynein light chain roadblock-type 1/2 / Methylated DNA-protein cysteine methyltransferase domain superfamily / Methylated-DNA-[protein]-cysteine S-methyltransferase, active site / Methylated-DNA--protein-cysteine methyltransferase active site. / Methylated-DNA-[protein]-cysteine S-methyltransferase, DNA binding ... Cytoplasmic dynein 2 intermediate chain 1 / : / Cytoplasmic dynein 2 heavy chain 1, AAA+ ATPase domain / Methylguanine DNA methyltransferase, ribonuclease-like domain / 6-O-methylguanine DNA methyltransferase, ribonuclease-like domain / Dynein light chain roadblock-type 1/2 / Methylated DNA-protein cysteine methyltransferase domain superfamily / Methylated-DNA-[protein]-cysteine S-methyltransferase, active site / Methylated-DNA--protein-cysteine methyltransferase active site. / Methylated-DNA-[protein]-cysteine S-methyltransferase, DNA binding / Methylated DNA-protein cysteine methyltransferase, DNA binding domain / : / 6-O-methylguanine DNA methyltransferase, DNA binding domain / Dynein light chain, type 1/2, conserved site / Dynein light chain type 1 signature. / Dynein light chain type 1 / Dynein light chain, type 1/2 / Dynein light chain superfamily / Dynein light chain type 1 / Roadblock/LAMTOR2 domain / Roadblock/LC7 domain / Roadblock/LC7 domain / 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 / Trp-Asp (WD) repeats circular profile. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / Winged helix-like DNA-binding 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 Methylated-DNA--protein-cysteine methyltransferase / Dynein light chain 1, cytoplasmic / Cytoplasmic dynein 2 heavy chain 1 / Cytoplasmic dynein 2 intermediate chain 1 / Cytoplasmic dynein 2 intermediate chain 2 / Dynein light chain roadblock-type 1 類似検索 - 構成要素生物種 Homo sapiens (ヒト)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 4.0 Å 詳細 データ登録者Mukhopadhyay AG / Toropova K / Daly L / Wells J / Vuolo L / Mladenov M / Seda M / Jenkins D / Stephens DJ / Roberts AJ 資金援助 英国, 9件 詳細 詳細を隠すOrganization Grant number 国 Wellcome Trust 217186/Z/19/Z 英国 Wellcome Trust 206166/Z/17/Z 英国 Wellcome Trust 202679/Z/16/Z 英国 Biotechnology and Biological Sciences Research Council (BBSRC) BB/P008348/1 英国 Biotechnology and Biological Sciences Research Council (BBSRC) BB/S007202/1 英国 Royal Society RG170260 英国 Biotechnology and Biological Sciences Research Council (BBSRC) BB/S013024/1 英国 Biotechnology and Biological Sciences Research Council (BBSRC) BB/S005390/1 英国 Wellcome Trust 210585/Z/18/Z 英国
引用ジャーナル : EMBO J / 年 : 2024タイトル : Structure and tethering mechanism of dynein-2 intermediate chains in intraflagellar transport.著者 : Aakash G Mukhopadhyay / Katerina Toropova / Lydia Daly / Jennifer N Wells / Laura Vuolo / Miroslav Mladenov / Marian Seda / Dagan Jenkins / David J Stephens / Anthony J Roberts / 要旨 : Dynein-2 is a large multiprotein complex that powers retrograde intraflagellar transport (IFT) of cargoes within cilia/flagella, but the molecular mechanism underlying this function is still emerging. ... Dynein-2 is a large multiprotein complex that powers retrograde intraflagellar transport (IFT) of cargoes within cilia/flagella, but the molecular mechanism underlying this function is still emerging. Distinctively, dynein-2 contains two identical force-generating heavy chains that interact with two different intermediate chains (WDR34 and WDR60). Here, we dissect regulation of dynein-2 function by WDR34 and WDR60 using an integrative approach including cryo-electron microscopy and CRISPR/Cas9-enabled cell biology. A 3.9 Å resolution structure shows how WDR34 and WDR60 use surprisingly different interactions to engage equivalent sites of the two heavy chains. We show that cilia can assemble in the absence of either WDR34 or WDR60 individually, but not both subunits. Dynein-2-dependent distribution of cargoes depends more strongly on WDR60, because the unique N-terminal extension of WDR60 facilitates dynein-2 targeting to cilia. Strikingly, this N-terminal extension can be transplanted onto WDR34 and retain function, suggesting it acts as a flexible tether to the IFT "trains" that assemble at the ciliary base. We discuss how use of unstructured tethers represents an emerging theme in IFT train interactions. 履歴 登録 2023年12月13日 - ヘッダ(付随情報) 公開 2024年3月20日 - マップ公開 2024年3月20日 - 更新 2024年4月10日 - 現状 2024年4月10日 処理サイト : PDBe / 状態 : 公開
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