title: Interdomain communication in the endonuclease/motor subunit of type I restriction-modification enzyme EcoR124I.
abstract: Restriction-modification systems protect bacteria from foreign DNA. Type I restriction-modification enzymes are multifunctional heteromeric complexes with DNA-cleavage and ATP-dependent DNA translocation activities located on endonuclease/motor subunit HsdR. The recent structure of the first intact motor subunit of the type I restriction enzyme from plasmid EcoR124I suggested a mechanism by which stalled translocation triggers DNA cleavage via a lysine residue on the endonuclease domain that contacts ATP bound between the two helicase domains. In the present work, molecular dynamics simulations are used to explore this proposal. Molecular dynamics simulations suggest that the Lys-ATP contact alternates with a contact with a nearby loop housing the conserved QxxxY motif that had been implicated in DNA cleavage. This model is tested here using in vivo and in vitro experiments. The results indicate how local interactions are transduced to domain motions within the endonuclease/motor subunit.
authors: Institute of Nanobiology and Structural Biology, Global Change Research Center, Academy of Sciences of the Czech Republic, Zamek 136, 373 33, Nove Hrady, Czech Republic.
authors: Dhiraj
authors: D
authors: Sinha
authors: Katsiaryna
authors: K
authors: Shamayeva
authors: Vyas
authors: V
authors: Ramasubramani
authors: David
authors: D
authors: Řeha
authors: Vitali
authors: V
authors: Bialevich
authors: Morteza
authors: M
authors: Khabiri
authors: Alena
authors: A
authors: Guzanová
authors: Niv
authors: N
authors: Milbar
authors: Marie
authors: M
authors: Weiserová
authors: Eva
authors: E
authors: Csefalvay
authors: Jannette
authors: J
authors: Carey
authors: Rüdiger
authors: R
authors: Ettrich
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism*; D020816:Amino Acid Motifs; D001665:Binding Sites; D002384:Catalysis; D017124:Conserved Sequence; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D015253:Deoxyribonucleases, Type I Site-Specific / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D006868:Hydrolysis; D007700:Kinetics; D008239:Lysine; D056004:Molecular Dynamics Simulation; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010641:Phenotype; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011789:Quantum Theory; D013329:Structure-Activity Relationship
chemical_list: D000255:Adenosine Triphosphate; D004247:DNA; C048242:endodeoxyribonuclease EcoR124I; D015253:Deoxyribonucleases, Type I Site-Specific; D008239:Lysine