Structure Reveals Mechanisms of Viral Suppressors that Intercept a CRISPR RNA-Guided Surveillance Complex

Cell. 2017 Mar 23;169(1):47-57.e11. doi: 10.1016/j.cell.2017.03.012.

Abstract

Genetic conflict between viruses and their hosts drives evolution and genetic innovation. Prokaryotes evolved CRISPR-mediated adaptive immune systems for protection from viral infection, and viruses have evolved diverse anti-CRISPR (Acr) proteins that subvert these immune systems. The adaptive immune system in Pseudomonas aeruginosa (type I-F) relies on a 350 kDa CRISPR RNA (crRNA)-guided surveillance complex (Csy complex) to bind foreign DNA and recruit a trans-acting nuclease for target degradation. Here, we report the cryo-electron microscopy (cryo-EM) structure of the Csy complex bound to two different Acr proteins, AcrF1 and AcrF2, at an average resolution of 3.4 Å. The structure explains the molecular mechanism for immune system suppression, and structure-guided mutations show that the Acr proteins bind to residues essential for crRNA-mediated detection of DNA. Collectively, these data provide a snapshot of an ongoing molecular arms race between viral suppressors and the immune system they target.

Keywords: Acr; CRISPR; CRISPR-Cas; Cas; Csy; anti-CRISPRs; crRNA; cryo-EM; cryo-electron microscopy; type I-F.

MeSH terms

  • Bacteriophages / chemistry*
  • Bacteriophages / classification
  • Bacteriophages / genetics
  • CRISPR-Associated Proteins / chemistry*
  • Clustered Regularly Interspaced Short Palindromic Repeats*
  • Cryoelectron Microscopy
  • Crystallography, X-Ray
  • Immunologic Surveillance
  • Models, Molecular
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / immunology*
  • Pseudomonas aeruginosa / virology*
  • RNA, Bacterial / chemistry*
  • RNA, Bacterial / metabolism
  • RNA, Bacterial / ultrastructure
  • Viral Proteins / chemistry*
  • Viral Proteins / ultrastructure

Substances

  • CRISPR-Associated Proteins
  • RNA, Bacterial
  • Viral Proteins