TitleStructure-based mechanism for activation of the AAA+ GTPase McrB by the endonuclease McrC.
Publication TypeJournal Article
Year of Publication2019
AuthorsNirwan N, Itoh Y, Singh P, Bandyopadhyay S, Vinothkumar KR, Amunts A, Saikrishnan K
JournalNat Commun
Date Published2019 Jul 11

The AAA+ GTPase McrB powers DNA cleavage by the endonuclease McrC. The GTPase itself is activated by McrC. The architecture of the GTPase and nuclease complex, and the mechanism of their activation remained unknown. Here, we report a 3.6 Å structure of a GTPase-active and DNA-binding deficient construct of McrBC. Two hexameric rings of McrB are bridged by McrC dimer. McrC interacts asymmetrically with McrB protomers and inserts a stalk into the pore of the ring, reminiscent of the γ subunit complexed to αβ of F-ATPase. Activation of the GTPase involves conformational changes of residues essential for hydrolysis. Three consecutive nucleotide-binding pockets are occupied by the GTP analogue 5'-guanylyl imidodiphosphate and the next three by GDP, which is suggestive of sequential GTP hydrolysis.

Alternate JournalNat Commun
PubMed ID31296862
PubMed Central IDPMC6624300
Grant ListEMR/2016/000872 / / Department of Science and Technology, Ministry of Science and Technology (DST) /