RuvBL1 and RuvBL2, also known as Pontin and Reptin, are AAA+ proteins essential in small nucleolar ribonucloprotein biogenesis, chromatin remodelling, nonsense-mediated messenger RNA decay and telomerase assembly, among other functions. They are homologous to prokaryotic RuvB, forming single- and double-hexameric rings; however, a DNA binding domain II (DII) is inserted within the AAA+ core. Despite their biological significance, questions remain regarding their structure. Here, we report cryo-electron microscopy structures of human double-ring RuvBL1–RuvBL2 complexes at ∼15 Å resolution. Significantly, we resolve two coexisting conformations, compact and stretched, by image classification techniques. Movements in DII domains drive these conformational transitions, extending the complex and regulating the exposure of DNA binding regions. DII domains connect with the AAA+ core and bind nucleic acids, suggesting that these conformational changes could impact the regulation of RuvBL1–RuvBL2 containing complexes. These findings resolve some of the controversies in the structure of RuvBL1–RuvBL2 by revealing a mechanism that extends the complex by adjustments in DII.

HighlightsMutations in C3 have been associated with aHUS and other glomerulopathies.aHUS-associated C3 mutants R592W, R161W, and I1157T impair regulation by MCP, but not by FH.EM analysis provides the structural basis for the functional impairment of the R161W and I1157T mutants.Data supports aHUS-associated C3 mutations selectively affect complement regulation on surfaces.

Background: Oligomerization of transcription factor YY1 is not well understood. Results: YY1 assembles homo-oligomers that bind DNAs without the consensus sequence, whose structure is studied by electron microscopy. Conclusion: RuvBL1-RuvBL2 enhances YY1 binding to DNAs without the consensus sequence for the transcription factor. Significance: YY1-RuvBL1-RuvBL2 complexes could contribute to functions beyond transcription, and we find this occurs during homologous recombination.