Summary information and primary citation
- PDB-id
- 8q3w; SNAP-derived features in text and JSON formats;
DNAproDB
- Class
- DNA binding protein
- Method
- cryo-EM (3.18 Å)
- Summary
- Atp-bound istb in complex to duplex DNA
- Reference
- de la Gandara A, Spinola-Amilibia M, Araujo-Bazan L, Nunez-Ramirez R, Berger JM, Arias-Palomo E (2024): "Molecular basis for transposase activation by a dedicated AAA+ ATPase." Nature, 630, 1003-1011. doi: 10.1038/s41586-024-07550-6.
- Abstract
- Transposases drive chromosomal rearrangements and the dissemination of drug-resistance genes and toxins1-3. 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.
