Aboard the ISS: intersubunit signaling revealed in the p97 ATPase

Abstract

A new cryo-EM study reveals how ATP hydrolysis in the p97 ATPase is coordinated to unfold the protein's substrates and provides new foundations for the design of small molecule therapeutics targeting p97 in cancer, neurodegeneration and viral infection.

A non-symmetrical p97 conformation initiates a multistep recruitment of Ufd1/Npl4

“…ATP binding in the downed NTD may occur, following the initiation of unfolding and staircase arrangement, as was previously reported. 25 , 34 , 41 , 43 , 45 Notably, heterogeneous NTD conformations associated with specific adaptors have been reported in other type-II AAA ATPases, 46 thus further evaluations are required to establish if these conformations may serve as preferential binding of specific adaptors.…”