pycsar.md

title: Pycsar
layout: article
tableColumns:
    article:
      doi: 10.1016/j.cell.2021.09.031
      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.
    Sensor: Unknown
    Activator: Signaling molecules
    Effector: Membrane disrupting, Nucleotides modifying
    PFAM: PF00004, PF00027, PF00211, PF00899, PF01734, PF10137, PF14461, PF14464, PF18145, PF18153, PF18303, PF18967

Pycsar

Example of genomic structure

The Pycsar is composed of at least 2 proteins: a Cyclase and Effector.

Like the CBASS system, it can encode for a variety of different effectors.

Here is an example found in the RefSeq database:

The Pycsar system in Nocardioides sambongensis (GCF_006494815.1, NZ_CP041091) is composed of 2 proteins 2TM_5 (WP_141014207.1) AG_cyclase (WP_141014208.1)

Distribution of the system among prokaryotes

Among the 22,803 complete genomes of RefSeq, the Pycsar is detected in 552 genomes (2.42 %).

The system was detected in 295 different species.

Proportion of genome encoding the Pycsar system for the 14 phyla with more than 50 genomes in the RefSeq database.

Structure

Pycsar

Example 1: ::molstar-pdbe-plugin

height: 700 dataUrl: /pycsar/Pycsar,CBASS__TIR,0,V-plddts_90.36719.pdb

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::molstar-pdbe-plugin

height: 700 dataUrl: /pycsar/Pycsar,Pycsar__AG_cyclase,0,V-plddts_94.90778.pdb

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Example 2: ::molstar-pdbe-plugin

height: 700 dataUrl: /pycsar/Pycsar,CBASS__TIR,0,V-plddts_90.36719.pdb

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::molstar-pdbe-plugin

height: 700 dataUrl: /pycsar/Pycsar,Pycsar__AG_cyclase,0,V-plddts_94.90778.pdb

::

Experimental validation

graph LR; Tal_2021[Tal et al., 2021] --> Origin_0 Origin_0[Escherichia coli 2684943848, 2742823945] --> Expressed_0[Escherichia coli] Expressed_0[Escherichia coli] ----> T5 & P1 & LambdaVir & SECphi27 Tal_2021[Tal et al., 2021] --> Origin_1 Origin_1[Xanthomonas perforans 2637229924, 2628816548] --> Expressed_1[Escherichia coli] Expressed_1[Escherichia coli] ----> T7 subgraph Title1[Reference] Tal_2021 end subgraph Title2[System origin] Origin_0 Origin_1 end subgraph Title3[Expression species] Expressed_0 Expressed_1 end subgraph Title4[Phage infected] T5 P1 LambdaVir SECphi27 T7 end style Title1 fill:none,stroke:none,stroke-width:none style Title2 fill:none,stroke:none,stroke-width:none style Title3 fill:none,stroke:none,stroke-width:none style Title4 fill:none,stroke:none,stroke-width:none ## Relevant abstracts

::relevant-abstracts

items: - doi: 10.1016/j.cell.2021.09.031

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