Structural highlights
FunctionPublication Abstract from PubMedTransposases drive chromosomal rearrangements and the dissemination of drug-resistance genes and toxins(1-3). Although some transposases act alone, many rely on dedicated AAA+ ATPase subunits that regulate site selectivity and catalytic function through poorly understood mechanisms. Using IS21 as a model transposase system, we show how an ATPase regulator uses nucleotide-controlled assembly and DNA deformation to enable structure-based site selectivity, transposase recruitment, and activation and integration. Solution and cryogenic electron microscopy studies show that the IstB ATPase self-assembles into an autoinhibited pentamer of dimers that tightly curves target DNA into a half-coil. Two of these decamers dimerize, which stabilizes the target nucleic acid into a kinked S-shaped configuration that engages the IstA transposase at the interface between the two IstB oligomers to form an approximately 1 MDa transpososome complex. Specific interactions stimulate regulator ATPase activity and trigger a large conformational change on the transposase that positions the catalytic site to perform DNA strand transfer. These studies help explain how AAA+ ATPase regulators-which are used by classical transposition systems such as Tn7, Mu and CRISPR-associated elements-can remodel their substrate DNA and cognate transposases to promote function. Molecular basis for transposase activation by a dedicated AAA+ ATPase.,de la Gandara A, Spinola-Amilibia M, Araujo-Bazan L, Nunez-Ramirez R, Berger JM, Arias-Palomo E Nature. 2024 Jun;630(8018):1003-1011. doi: 10.1038/s41586-024-07550-6. Epub 2024 , Jun 26. PMID:38926614[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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