An Atypical AAA+ ATPase Assembly Controls Efficient Transposition through DNA Remodeling and Transposase Recruitment

• IstB, an AAA+ DNA transposition regulator, assembles into a clamshell-shaped decamer
• Two pentameric lobes of the IstB decamer sandwich and bend DNA by 180°
• IstA recognizes and dissociates IstB
• DNA complexes by stimulating ATP hydrolysis

SummaryTransposons are ubiquitous genetic elements that drive genome rearrangements, evolution, and the spread of infectious disease and drug-resistance. Many transposons, such as Mu, Tn7, and IS21, require regulatory AAA+ ATPases for function. We use X-ray crystallography and cryo-electron microscopy to show that the ATPase subunit of IS21, IstB, assembles into a clamshell-shaped decamer that sandwiches DNA between two helical pentamers of ATP-associated AAA+ domains, sharply bending the duplex into a 180° U-turn. Biochemical studies corroborate key features of the structure and further show that the IS21 transposase, IstA, recognizes the IstB
• DNA complex and promotes its disassembly by stimulating ATP hydrolysis. Collectively, these studies reveal a distinct manner of higher-order assembly and client engagement by a AAA+ ATPase and suggest a mechanistic model where IstB binding and subsequent DNA bending primes a selected insertion site for efficient transposition.

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