- PDB-6zy6: Cryo-EM structure of the Human topoisomerase II alpha DNA-binding... -
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基本情報
登録情報
データベース: PDB / ID: 6zy6
タイトル
Cryo-EM structure of the Human topoisomerase II alpha DNA-binding/cleavage domain in State 2
要素
DNA (5'-D(*CP*GP*CP*GP*CP*AP*TP*CP*GP*TP*CP*AP*TP*CP*CP*TP*C)-3')
DNA (5'-D(*GP*AP*GP*GP*AP*TP*GP*AP*CP*GP*AP*TP*G)-3')
DNA topoisomerase 2-alpha
キーワード
ISOMERASE / Human Topoisomerase / Etoposide / DNA
機能・相同性
機能・相同性情報
negative regulation of DNA duplex unwinding / positive regulation of single stranded viral RNA replication via double stranded DNA intermediate / sister chromatid segregation / apoptotic chromosome condensation / resolution of meiotic recombination intermediates / female meiotic nuclear division / DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) complex / embryonic cleavage / DNA ligation / Transcription of E2F targets under negative control by DREAM complex ...negative regulation of DNA duplex unwinding / positive regulation of single stranded viral RNA replication via double stranded DNA intermediate / sister chromatid segregation / apoptotic chromosome condensation / resolution of meiotic recombination intermediates / female meiotic nuclear division / DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) complex / embryonic cleavage / DNA ligation / Transcription of E2F targets under negative control by DREAM complex / DNA binding, bending / DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity / DNA topoisomerase (ATP-hydrolysing) / condensed chromosome / DNA topological change / SUMOylation of DNA replication proteins / chromosome, centromeric region / ATP-dependent activity, acting on DNA / male germ cell nucleus / hematopoietic progenitor cell differentiation / ubiquitin binding / chromosome segregation / regulation of circadian rhythm / protein kinase C binding / rhythmic process / ribonucleoprotein complex / protein heterodimerization activity / positive regulation of apoptotic process / chromatin binding / DNA damage response / nucleolus / magnesium ion binding / positive regulation of transcription by RNA polymerase II / protein homodimerization activity / protein-containing complex / DNA binding / RNA binding / nucleoplasm / ATP binding / nucleus / cytoplasm 類似検索 - 分子機能
DTHCT / DTHCT (NUC029) region / DNA topoisomerase 2, TOPRIM domain / : / DNA topoisomerase II, eukaryotic-type / C-terminal associated domain of TOPRIM / C-terminal associated domain of TOPRIM / Topoisomerase (Topo) IIA-type catalytic domain profile. / DNA topoisomerase, type IIA, alpha-helical domain superfamily / DNA topoisomerase, type IIA, domain A ...DTHCT / DTHCT (NUC029) region / DNA topoisomerase 2, TOPRIM domain / : / DNA topoisomerase II, eukaryotic-type / C-terminal associated domain of TOPRIM / C-terminal associated domain of TOPRIM / Topoisomerase (Topo) IIA-type catalytic domain profile. / DNA topoisomerase, type IIA, alpha-helical domain superfamily / DNA topoisomerase, type IIA, domain A / DNA topoisomerase, type IIA, domain A, alpha-beta / DNA gyrase/topoisomerase IV, subunit A / DNA Topoisomerase IV / DNA topoisomerase, type IIA, subunit B, domain 2 / DNA gyrase B / DNA topoisomerase, type IIA / DNA topoisomerase, type IIA, conserved site / DNA topoisomerase II signature. / TopoisomeraseII / DNA topoisomerase, type IIA, subunit B, C-terminal / Toprim domain / DNA topoisomerase, type IIA-like domain superfamily / Toprim domain profile. / TOPRIM domain / Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase / Histidine kinase/HSP90-like ATPase / Histidine kinase/HSP90-like ATPase superfamily / Ribosomal protein S5 domain 2-type fold, subgroup / Ribosomal protein S5 domain 2-type fold 類似検索 - ドメイン・相同性
Chem-EVP / DNA / DNA (> 10) / DNA topoisomerase 2-alpha 類似検索 - 構成要素
French Infrastructure for Integrated Structural Biology (FRISBI)
FRISBI ANR-10-INBS-05
フランス
引用
ジャーナル: Nat Commun / 年: 2021 タイトル: Structural basis for allosteric regulation of Human Topoisomerase IIα. 著者: Arnaud Vanden Broeck / Christophe Lotz / Robert Drillien / Léa Haas / Claire Bedez / Valérie Lamour / 要旨: The human type IIA topoisomerases (Top2) are essential enzymes that regulate DNA topology and chromosome organization. The Topo IIα isoform is a prime target for antineoplastic compounds used in ...The human type IIA topoisomerases (Top2) are essential enzymes that regulate DNA topology and chromosome organization. The Topo IIα isoform is a prime target for antineoplastic compounds used in cancer therapy that form ternary cleavage complexes with the DNA. Despite extensive studies, structural information on this large dimeric assembly is limited to the catalytic domains, hindering the exploration of allosteric mechanism governing the enzyme activities and the contribution of its non-conserved C-terminal domain (CTD). Herein we present cryo-EM structures of the entire human Topo IIα nucleoprotein complex in different conformations solved at subnanometer resolutions (3.6-7.4 Å). Our data unveils the molecular determinants that fine tune the allosteric connections between the ATPase domain and the DNA binding/cleavage domain. Strikingly, the reconstruction of the DNA-binding/cleavage domain uncovers a linker leading to the CTD, which plays a critical role in modulating the enzyme's activities and opens perspective for the analysis of post-translational modifications.
A: DNA topoisomerase 2-alpha B: DNA topoisomerase 2-alpha D: DNA (5'-D(*CP*GP*CP*GP*CP*AP*TP*CP*GP*TP*CP*AP*TP*CP*CP*TP*C)-3') E: DNA (5'-D(*GP*AP*GP*GP*AP*TP*GP*AP*CP*GP*AP*TP*G)-3') F: DNA (5'-D(*CP*GP*CP*GP*CP*AP*TP*CP*GP*TP*CP*AP*TP*CP*CP*TP*C)-3') C: DNA (5'-D(*GP*AP*GP*GP*AP*TP*GP*AP*CP*GP*AP*TP*G)-3') ヘテロ分子