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bioRxiv · 10.1101/2022.02.23.481423

Metamorphism of catalytic domain controls transposition in Tn3 family transposases

Shkumatov, A. V.·Aryanpour, N.·Oger, C. A.·Goossens, G.·Hallet, B. F.·Efremov, R. G.
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Abstract

Transposons account for a remarkable diversity of mobile genetic elements that play the role of genome architects in all domains of life. Tn3 is a family of widespread and among first identified bacterial transposons notorious for their contribution to dissemination of antibiotic resistance. Transposition within this family is mediated by a large TnpA transposase facilitating both transposition and target immunity. The structural framework for understanding the mechanism of the TnpA transposition is however absent. Here, we describe the cryo-EM structures of TnpA from Tn4430 in apo form and paired with transposon ends. We show that TnpA has a unique architecture and exhibits a family-specific regulation mechanism involving metamorphic refolding of the RNase H-like catalytic domain. The TnpA structure, constrained by a double dimerization interface, creates a unique topology that suggests a specific role for target DNA in transpososome assembly, activation, and target immunity.

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Shkumatov, A. V., Aryanpour, N., Oger, C. A., Goossens, G., Hallet, B. F., Efremov, R. G.. 2022-02-24. Metamorphism of catalytic domain controls transposition in Tn3 family transposases. https://doi.org/10.1101/2022.02.23.481423

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