Structure Reveals Mechanisms of Viral Suppressors that Intercept a CRISPR RNA-Guided Surveillance Complex
| Autor: | Lyn'Al Nosaka, Karen L. Maxwell, Joshua Carter, MaryClare F. Rollins, Sarah Golden, Elizabeth R. Fischer, Joseph Bondy-Denomy, Connor Hoffmann, Gabriel C. Lander, Alan R. Davidson, Saikat Chowdhury, Ryan N. Jackson, Blake Wiedenheft |
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| Rok vydání: | 2017 |
| Předmět: |
Models
Molecular 0301 basic medicine CRISPR-Associated Proteins Immunologic Surveillance Crystallography X-Ray Medical and Health Sciences chemistry.chemical_compound Models CRISPR Bacteriophages Clustered Regularly Interspaced Short Palindromic Repeats CRISPR-Cas crRNA Genetics Crystallography Bacterial Cas Biological Sciences type I-F Acquired immune system 3. Good health RNA Bacterial Infectious Diseases Pseudomonas aeruginosa Infection 1.1 Normal biological development and functioning cryo-electron microscopy Biology Article General Biochemistry Genetics and Molecular Biology Viral Proteins 03 medical and health sciences Rare Diseases Immune system Underpinning research Trans-activating crRNA Nuclease Acr Csy Inflammatory and immune system Cryoelectron Microscopy Molecular RNA Emerging Infectious Diseases Good Health and Well Being 030104 developmental biology chemistry X-Ray biology.protein cryo-EM anti-CRISPRs DNA Developmental Biology |
| Zdroj: | Cell, vol 169, iss 1 |
| ISSN: | 0092-8674 |
| Popis: | Genetic conflict between viruses and their hosts drives evolution and genetic innovation. Prokaryotes evolved CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat)-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 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. |
| Databáze: | OpenAIRE |
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