Michael Prattes, Mathias Loibl, Gertrude Zisser, Daniel Luschnig, Lisa Kappel, Ingrid Rössler, Manuela Grassegger, Altijana Hromic, Elmar Krieger, Karl Gruber, Brigitte Pertschy and Helmut Bergler.
Scientific Reports, 7:44751
A conserved inter-domain communication mechanism regulates the ATPase activity of the AAA-protein Drg1
The yeast ribosome biogenesis factor Drg1 and the multifunctional mammalian protein p97 are both members of the widespread enzyme family of AAA-ATPases. Although they act in different cellular pathways their enzymatic domains are still conserved. In this study we characterized mutant variants of Drg1 with amino acid exchanges at the interface between the D1 domain (one of two ATPase domains) and the regulatory N-terminal domain. The regulatory defects caused by these mutations resemble those of mutations in p97 that cause the hereditary syndrome IBMPFD. The finding that similar mutations in both proteins disturb regulation of ATPase activity was surprising based on the low sequence conservation of the N-domain. This indicates that these functionally diverged proteins still use similar mechanisms to regulate their enzymatic activity.