From 3b2243bfc1330366b9280f9b901d89c1adba3bc7 Mon Sep 17 00:00:00 2001
From: Aude BERNHEIM <aude.bernheim@pasteur.fr>
Date: Tue, 28 Nov 2023 12:44:24 +0100
Subject: [PATCH] Update dgtpase.md
---
content/3.defense-systems/dgtpase.md | 31 ++++++++++++++--------------
1 file changed, 16 insertions(+), 15 deletions(-)
diff --git a/content/3.defense-systems/dgtpase.md b/content/3.defense-systems/dgtpase.md
index 9c346e97..208c3406 100644
--- a/content/3.defense-systems/dgtpase.md
+++ b/content/3.defense-systems/dgtpase.md
@@ -3,23 +3,34 @@ title: dGTPase
layout: article
tableColumns:
article:
- doi: 10.1016/j.cell.2021.09.031
+ doi: 10.1038/s41564-022-01158-0
abstract: |
- The cyclic pyrimidines 3',5'-cyclic cytidine monophosphate (cCMP) and 3',5'-cyclic uridine monophosphate (cUMP) have been reported in multiple organisms and cell types. As opposed to the cyclic nucleotides 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP), which are second messenger molecules with well-established regulatory roles across all domains of life, the biological role of cyclic pyrimidines has remained unclear. Here we report that cCMP and cUMP are second messengers functioning in bacterial immunity against viruses. We discovered a family of bacterial pyrimidine cyclase enzymes that specifically synthesize cCMP and cUMP following phage infection and demonstrate that these molecules activate immune effectors that execute an antiviral response. A crystal structure of a uridylate cyclase enzyme from this family explains the molecular mechanism of selectivity for pyrimidines as cyclization substrates. Defense systems encoding pyrimidine cyclases, denoted here Pycsar (pyrimidine cyclase system for antiphage resistance), are widespread in prokaryotes. Our results assign clear biological function to cCMP and cUMP as immunity signaling molecules in bacteria.
+ DNA viruses and retroviruses consume large quantities of deoxynucleotides (dNTPs) when replicating. The human antiviral factor SAMHD1 takes advantage of this vulnerability in the viral lifecycle, and inhibits viral replication by degrading dNTPs into their constituent deoxynucleosides and inorganic phosphate. Here, we report that bacteria use a similar strategy to defend against bacteriophage infection. We identify a family of defensive bacterial deoxycytidine triphosphate (dCTP) deaminase proteins that convert dCTP into deoxyuracil nucleotides in response to phage infection. We also identify a family of phage resistance genes that encode deoxyguanosine triphosphatase (dGTPase) enzymes, which degrade dGTP into phosphate-free deoxyguanosine and are distant homologues of human SAMHD1. Our results suggest that bacterial defensive proteins deplete specific deoxynucleotides (either dCTP or dGTP) from the nucleotide pool during phage infection, thus starving the phage of an essential DNA building block and halting its replication. Our study shows that manipulation of the dNTP pool is a potent antiviral strategy shared by both prokaryotes and eukaryotes.
Sensor: Monitoring of the host cell machinery integrity
- Activator: Direc
+ Activator: Direct
Effector: Nucleotide modifying
PFAM: PF01966, PF13286
+contributors:
+ - Aude Bernheim
+relevantAbstracts:
+ - doi: 10.1038/s41564-022-01158-0
---
# dGTPase
+
+## Description
+dGTPase are a family of proteins discovered in :ref{doi=10.1038/s41564-022-01158-0}. It degrades dGTP into phosphate-free deoxyguanosine. It was suggested that these *"bacterial defensive proteins deplete deoxynucleotides from the nucleotide pool during phage infection, thus starving the phage of an essential DNA building block and halting its replication"*. The mechanism is remindful of the mechanism of SAMHD1 in humans.
+
+## Molecular mechanism
+dGTPase degrades dGTP into phosphate-free deoxyguanosine. Phage mutants which overcome this defense carry mutations in phage-RNAP-modifying proteins suggesting, that *"phage-mediated inhibition of host transcription may be involved in triggering the activation of bacterial dNTP-depletion"*.
+
## Example of genomic structure
The dGTPase system is composed of one protein: Sp_dGTPase.
Here is an example found in the RefSeq database:
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+{max-width=750px}
dGTPase system in the genome of *Acinetobacter pittii* (GCF_002012285.1) is composed of 1 protein: Sp_dGTPase (WP_213033921.1).
@@ -29,7 +40,7 @@ The dGTPase system is present in a total of 353 different species.
Among the 22k complete genomes of RefSeq, this system is present in 1532 genomes (6.7 %).
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+{max-width=750px}
*Proportion of genome encoding the dGTPase system for the 14 phyla with more than 50 genomes in the RefSeq database.*
@@ -111,13 +122,3 @@ end
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-## Relevant abstracts
-
-::relevant-abstracts
----
-items:
- - doi: 10.1038/s41564-022-01162-4
-
----
-::
-
--
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