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Remi PLANEL authoredRemi PLANEL authored
- Avs
- Description
- Molecular mechanism
- Example of genomic structure
- Distribution of the system among prokaryotes
- Structure
- AVAST_I
- Example 1
- ::molstar-pdbe-plugin
- AVAST_II
- Example 1
- ::molstar-pdbe-plugin
- AVAST_III
- Example 1
- ::molstar-pdbe-plugin
- AVAST_IV
- Example 1
- ::molstar-pdbe-plugin
- AVAST_V
- Example 1
- ::molstar-pdbe-plugin
- Experimental validation
title: Avs
layout: article
tableColumns:
article:
doi: 10.1126/science.aba0372
abstract: |
Bacteria and archaea are frequently attacked by viruses and other mobile genetic elements and rely on dedicated antiviral defense systems, such as restriction endonucleases and CRISPR, to survive. The enormous diversity of viruses suggests that more types of defense systems exist than are currently known. By systematic defense gene prediction and heterologous reconstitution, here we discover 29 widespread antiviral gene cassettes, collectively present in 32% of all sequenced bacterial and archaeal genomes, that mediate protection against specific bacteriophages. These systems incorporate enzymatic activities not previously implicated in antiviral defense, including RNA editing and retron satellite DNA synthesis. In addition, we computationally predict a diverse set of other putative defense genes that remain to be characterized. These results highlight an immense array of molecular functions that microbes use against viruses.
Sensor: Sensing of phage protein
Activator: Direct binding
Effector: Diverse effectors (Nucleic acid degrading, putative Nucleotide modifying, putative Membrane disrupting)
PFAM: PF00753, PF13289, PF13365
contributors:
- Alex Linyi Gao
- Nathalie Bechon
relevantAbstracts:
- doi: 10.1126/science.aba0372
- doi: 10.1126/science.abm4096Avs
Description
Avs proteins are members of the STAND (signal transduction ATPase with numerous domains) superfamily of P-loop NTPases, which play essential roles in innate immunity and programmed cell death in eukaryotes :ref{doi=10.1038/sj.cdd.4400991,10.1016/j.jmb.2004.08.023}. STAND ATPases include nucleotide-binding oligomerization domain-like receptors (NLRs) in animal inflammasomes and plant resistosomes. Bacterial Avs share a common tripartite domain architecture with eukaryotic NLR, typically consisting of a central ATPase, a C-terminal sensor with superstructure-forming repeats, and an N-terminal effector involved in inflammation or cell death. They are very similar to other bacterial defense systems: bNACHT, CARD_NLR , Rst_TIR-NLR.
Molecular mechanism
::info Two classifications of Avs systems were proposed. The first one :ref{doi=10.1126/science.aba0372} distinguishes 5 types of Avs based on their effector domain. This is the classification used in Defense Finder right now, and in the following wiki entry unless stated otherwise. Considering the modular aspect of the effector domain, a new classification based on the homology of the NTPase and C terminal sensor domain, and not on the effector domain, has been proposed more recently :ref{doi=10.1126/science.abm4096} and is the one used in this description of the mechanism. This second classification defines 4 different types, that do not represent the whole diversity of Avs proteins but only the 4 characterized types. ::
Similar to their eukaryotic counterparts, Avs proteins utilize their C-terminal sensor domains to bind to pathogen-associated molecular patterns (PAMPs). Specifically, Avs1, Avs2, and Avs3 bind to monomers of the large terminase subunit of tailed phages, which account for approximately 96% of all phages, whereas Avs4 binds to monomers of the portal protein. The helical sensor domains of Avs1-4 can recognize diverse variants of terminase or portal proteins, with less than 5% sequence identity in some cases. Binding is mediated by shape complementarity across an extended interface, indicating fold recognition. Additionally, Avs3 directly recognizes active site residues and the ATP ligand of the large terminase.
Upon binding to their cognate phage protein, Avs1-4 assemble into tetramers that activate their N-terminal effector domains, which are often non-specific dsDNA endonucleases. The effector domains are thought to induce abortive infection to disrupt the production of progeny phage.
Avs systems sometimes include additional essential small genes on top of the canonical Avs gene, but the way they contribute to defense is not currently described.
Example of genomic structure
The Avs system has been described in a total of 5 subsystems (in the old classification).
Here are some examples found in the RefSeq database:
The Avs_I system in Priestia aryabhattai (GCF_022811825.1, NZ_CP064098) is composed of 3 proteins Avs1C (WP_243495694.1) Avs1B (WP_243495695.1) Avs1A (WP_243495696.1)
The Avs_II system in Haloferax volcanii (GCF_000025685.1, NC_013967) is composed of 1 protein: Avs2A (WP_013035348.1)
The Avs_III system in Chryseobacterium indologenes (GCF_002208925.2, NZ_CP022058) is composed of 2 proteins Avs3B (WP_002978689.1) Avs3A (WP_088583894.1)
The Avs_IV system in Dysosmobacter welbionis (GCF_005121165.3, NZ_CP034413) is composed of 1 protein: Avs4A (WP_136890703.1)
The Avs_V system in Klebsiella variicola (GCF_015287155.1, NZ_CP063912) is composed of 1 protein: Avs5A (WP_131026359.1)
Distribution of the system among prokaryotes
Among the 22,803 complete genomes of RefSeq, the Avs is detected in 978 genomes (4.29 %).
The system was detected in 366 different species.
Proportion of genome encoding the Avs system for the 14 phyla with more than 50 genomes in the RefSeq database.
::article-system-distribution-plot ::
Structure
AVAST_I
Example 1
::molstar-pdbe-plugin
height: 700 dataUrls:
- /avs/AVAST_I.AVAST_I__Avs1A.0.V.cif
- /avs/AVAST_I.AVAST_I__Avs1C.0.V.cif
- /avs/AVAST_I.AVAST_I__Avs1B.0.V.cif
::
AVAST_II
Example 1
::molstar-pdbe-plugin
height: 700 dataUrls:
- /avs/AVAST_II__Avs2A.cif
::
AVAST_III
Example 1
::molstar-pdbe-plugin
height: 700 dataUrls:
- /avs/AVAST_III.AVAST_III__Avs3B.0.V.cif
- /avs/AVAST_III.AVAST_III__Avs3A.0.V.cif
::
AVAST_IV
Example 1
::molstar-pdbe-plugin
height: 700 dataUrls:
- /avs/AVAST_IV__Avs4A.cif
::
AVAST_V
Example 1
::molstar-pdbe-plugin
height: 700 dataUrls:
- /avs/AVAST_V__Avs5A.cif
::