Topoisomerase I (TOP1) dynamics: conformational transition from open to closed states - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Nature Communications Année : 2022

Topoisomerase I (TOP1) dynamics: conformational transition from open to closed states

Résumé

Eukaryotic topoisomerases I (TOP1) are ubiquitous enzymes removing DNA torsional stress. However, there is little data concerning the three-dimensional structure of TOP1 in the absence of DNA, nor how the DNA molecule can enter/exit its closed conformation. Here, we solved the structure of thermostable archaeal Caldiarchaeum subterraneum CsTOP1 in an apo-form. The enzyme displays an open conformation resulting from one substantial rotation between the capping (CAP) and the catalytic (CAT) modules. The junction between these two modules is a five-residue loop, the hinge, whose flexibility permits the opening/closing of the enzyme and the entry of DNA. We identified a highly conserved tyrosine near the hinge as mediating the transition from the open to closed conformation upon DNA binding. Directed mutagenesis confirmed the importance of the hinge flexibility, and linked the enzyme dynamics with sensitivity to camptothecin, a TOP1 inhibitor targeting the TOP1 enzyme catalytic site in the closed conformation
Fichier principal
Vignette du fichier
s41467-021-27686-7.pdf (2.98 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03716980 , version 1 (07-07-2022)

Licence

Paternité

Identifiants

Citer

Diane Takahashi, Danièle Gadelle, Keli Agama, Evgeny Kiselev, Hongliang Zhang, et al.. Topoisomerase I (TOP1) dynamics: conformational transition from open to closed states. Nature Communications, 2022, 13 (1), pp.59. ⟨10.1038/s41467-021-27686-7⟩. ⟨hal-03716980⟩
32 Consultations
24 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More