Projects per year
Abstract
The CRISPR system provides adaptive immunity against mobile genetic
elements in prokaryotes. On binding invading RNA species, Type III
CRISPR systems generate cyclic oligoadenylate (cOA) signalling
molecules, potentiating a powerful immune response by activating
downstream effector proteins, leading to viral clearance, cell dormancy
or death. Here we describe the structure and mechanism of a
cOA-activated CRISPR defence DNA endonuclease, CRISPR ancillary nuclease
1 (Can1). Can1 has a unique monomeric structure with two CRISPR
associated Rossman fold (CARF) domains and two DNA nuclease-like
domains. The crystal structure of the enzyme has been captured in the
activated state, with a cyclic tetra-adenylate (cA4) molecule bound at the core of the protein. cA4
binding reorganises the structure to license a metal-dependent DNA
nuclease activity specific for nicking of supercoiled DNA. DNA nicking
by Can1 is predicted to slow down viral replication kinetics by leading
to the collapse of DNA replication forks.
Original language | English |
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Article number | 500 |
Number of pages | 11 |
Journal | Nature Communications |
Volume | 11 |
DOIs | |
Publication status | Published - 24 Jan 2020 |
Fingerprint
Dive into the research topics of 'Structure and mechanism of a Type III CRISPR defence DNA nuclease activated by cyclic oligoadenylate'. Together they form a unique fingerprint.Projects
- 2 Finished
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Cyclic oligoadenylate signalling: Cyclic oligoadenylate signalling - a new type of antiviral response
White, M. (PI)
1/01/19 → 31/12/21
Project: Standard
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Tracey Gloster: Understanding the activity and function of hexosaminidase D
Gloster, T. (PI)
1/04/18 → 30/09/21
Project: Standard
Profiles
Datasets
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Structure of a Type III CRISPR defence DNA nuclease activated by cyclic oligoadenylate
White, M. (Creator) & Gloster, T. (Creator), Protein Data Bank (PDB), 19 Feb 2020
DOI: 10.2210/pdb6SCE/pdb
Dataset