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-Structure paper
タイトル | Structural basis for allosteric regulation of Human Topoisomerase IIα. |
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ジャーナル・号・ページ | Nat Commun, Vol. 12, Issue 1, Page 2962, Year 2021 |
掲載日 | 2021年5月20日 |
著者 | Arnaud Vanden Broeck / Christophe Lotz / Robert Drillien / Léa Haas / Claire Bedez / Valérie Lamour / |
PubMed 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. |
リンク | Nat Commun / PubMed:34016969 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.6 - 7.6 Å |
構造データ | EMDB-11550, PDB-6zy5: EMDB-11551, PDB-6zy6: EMDB-11552: EMDB-11553, PDB-6zy7: EMDB-11554, PDB-6zy8: |
化合物 | ChemComp-EVP: ChemComp-ANP: |
由来 |
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キーワード | ISOMERASE / Human Topoisomerase / Etoposide / DNA |