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The mechanisms that regulate adenosine triphosphate (ATP)-dependent activity, oligomerization and post-translational modifications in this family of enzymes are yet unknown. We present the first crystallographic structure of full-length human RuvBL2 which provides novel insights into its mechanistic action and biology. The ring-shaped hexameric RuvBL2 structure presented here resolves for the first time the mobile domain II of the human protein, which is responsible for protein-protein interactions and ATPase activity regulation. Structural analysis suggests how ATP binding may lead to domain II motion through interactions with conserved N-terminal loop histidine residues. Furthermore, a comparison between <jats:italic>hs<\/jats:italic>RuvBL1 and 2 shows differences in surface charge distribution that may account for previously described differences in regulation. Analytical ultracentrifugation and cryo electron microscopy analyses performed on <jats:italic>hs<\/jats:italic>RuvBL2 highlight an oligomer plasticity that possibly reflects different physiological conformations of the protein in the cell, as well as that single-stranded DNA (ssDNA) can promote the oligomerization of monomeric <jats:italic>hs<\/jats:italic>RuvBL2. Based on these findings, we propose a mechanism for ATP binding and domain II conformational change coupling.<\/jats:p>","DOI":"10.1038\/s41598-018-31997-z","type":"journal-article","created":{"date-parts":[[2018,9,7]],"date-time":"2018-09-07T09:11:03Z","timestamp":1536311463000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["X-ray structure of full-length human RuvB-Like 2 \u2013 mechanistic insights into coupling between ATP binding and mechanical action"],"prefix":"10.1038","volume":"8","author":[{"given":"Sara T. 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