Fig. 6: MORC2 changes conformation upon ATP binding via heads dimerization. | Nature Communications

Fig. 6: MORC2 changes conformation upon ATP binding via heads dimerization.

From: MORC2 is a phosphorylation-dependent DNA compaction machine

Fig. 6: MORC2 changes conformation upon ATP binding via heads dimerization.The alternative text for this image may have been generated using AI.

a Representative dry-AFM image of MORC2 in the absence of ATP. b Representative images of the monomer (top) and dimer (bottom) forms of MORC2. Experiments were repeated independently three times for (a) and (b). c Distributions of MORC2 volume, showing two distinct peaks, indicating two populations of monomers and dimers. Two gaussian fitting was used. Cartoons and representative images illustrating various O-shape of the MORC2 dimer (d) and V-shape of MORC2 dimer (e) in absence of DNA. f Relative occurrence of O-shaped and V-shaped conformations (number of technical replicates (n) = 252, 1001, and 68 individual proteins with AMP-PNP, AMP and the N39A mutant, respectively). Error bars represent counting errors. Cartoons and representative image of the S87A (g) and N39A mutants bound to DNA (h). i Number of DNA-bound MORC2 proteins per unit DNA length under various conditions: the S87A mutant (n = 21), N39A mutant (n = 13), the 1–603 fragment (n = 5), and the 604–1032 fragment (n = 5). The centre line and bounds of the box represent the mean and SD, respectively. Cartoons and representative images of O-shaped WT ( j) and V-shaped WT (k) bound to DNA. l. Relative occurrence of O-shaped and V-shaped conformations bound to DNA (n = 119 molecules from 11 independent experiments and n = 35 molecules from 13 independent experiments with AMP-PNP and ATP, respectively). Error bars represent the counting errors for each protein shape. For (f), (i) and (l), the p-values were obtained by the one-tailed unpaired t-test. For (c), (f), (i) and (l), source data are provided as a Source Data file. m Model of DNA compaction mediated by MORC2 phosphorylation and ATP hydrolysis. A MORC2 molecule dimerised at CTD is shown, which subsequently gets dimerised at it NTD upon phosphorylation, DNA binding and ATP hydrolysis. Upon dephosphorylation, the DNA is clamped by MORC2 strongly. Eventually, another MORC2 molecule is recruited bringing in more DNA, thus leading to DNA compaction. For (an) the experiments were performed with two biological replicates. The panel m was created in BioRender. Tan, W. (2025) https://BioRender.com/11811kf.

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