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Nat Commun. 2019 Jul 11;10(1):3058. doi: 10.1038/s41467-019-11084-1.

Structure-based mechanism for activation of the AAA+ GTPase McrB by the endonuclease McrC.

Author information

1
Division of Biology, Indian Institute of Science Education and Research, Pune, 411008, India.
2
Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, 17165, Solna, Sweden.
3
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177, Stockholm, Sweden.
4
MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK.
5
National Centre for Biological Sciences-TIFR, GKVK Post, Bellary Road, Bangalore, 560065, India.
6
Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, 17165, Solna, Sweden. amunts@scilifelab.se.
7
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177, Stockholm, Sweden. amunts@scilifelab.se.
8
Division of Biology, Indian Institute of Science Education and Research, Pune, 411008, India. saikrishnan@iiserpune.ac.in.

Abstract

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 α3β3 of F1-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.

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