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The hexameric p97 enzyme plays an integral role in cellular homeostasis. Large changes to the orientation of its N‐terminal domains (NTDs), corresponding to NTD‐down (p97‐ADP) or NTD‐up (p97‐ATP), accompany ATP hydrolysis. The NTDs in a series of p97 disease mutants interconvert rapidly between up and down conformations when p97 is in the ADP‐bound state. While the populations of up and down NTDs...
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