Interdomain communication in the endonuclease/motor subunit of type I restriction-modification enzyme EcoR124I

Dhiraj Sinha; Katsiaryna Shamayeva; Vyas Ramasubramani; David Řeha; Vitali Bialevich; Morteza Khabiri; Alena Guzanová; Niv Milbar; Marie Weiserová; Eva Csefalvay; Jannette Carey; Rüdiger Ettrich

doi:10.1007/s00894-014-2334-1

Interdomain communication in the endonuclease/motor subunit of type I restriction-modification enzyme EcoR124I

Dhiraj Sinha, Katsiaryna Shamayeva, Vyas Ramasubramani, David Řeha, Vitali Bialevich, Morteza Khabiri, Alena Guzanová, Niv Milbar, Marie Weiserová, Eva Csefalvay, Jannette Carey, Rüdiger Ettrich

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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.

Original language	English (US)
Article number	2334
Journal	Journal of Molecular Modeling
Volume	20
Issue number	7
DOIs	https://doi.org/10.1007/s00894-014-2334-1
State	Published - Jul 2014

All Science Journal Classification (ASJC) codes

Catalysis
Inorganic Chemistry
Computer Science Applications
Physical and Theoretical Chemistry
Computational Theory and Mathematics
Organic Chemistry

Keywords

Correlated loop motions
DNA restriction enzymes
E. coli
Molecular modeling
Multisubunit enzyme complex
Principal components analysis
QM/MM calculations

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10.1007/s00894-014-2334-1

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Sinha, D., Shamayeva, K., Ramasubramani, V., Řeha, D., Bialevich, V., Khabiri, M., Guzanová, A., Milbar, N., Weiserová, M., Csefalvay, E., Carey, J., & Ettrich, R. (2014). Interdomain communication in the endonuclease/motor subunit of type I restriction-modification enzyme EcoR124I. Journal of Molecular Modeling, 20(7), Article 2334. https://doi.org/10.1007/s00894-014-2334-1

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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.",

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doi = "10.1007/s00894-014-2334-1",

language = "English (US)",

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AU - Sinha, Dhiraj

AU - Shamayeva, Katsiaryna

AU - Ramasubramani, Vyas

AU - Řeha, David

AU - Bialevich, Vitali

AU - Khabiri, Morteza

AU - Guzanová, Alena

AU - Milbar, Niv

AU - Weiserová, Marie

AU - Csefalvay, Eva

AU - Carey, Jannette

AU - Ettrich, Rüdiger

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N2 - 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.

AB - 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.

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KW - DNA restriction enzymes

KW - E. coli

KW - Molecular modeling

KW - Multisubunit enzyme complex

KW - Principal components analysis

KW - QM/MM calculations

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Interdomain communication in the endonuclease/motor subunit of type I restriction-modification enzyme EcoR124I

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