Defensive Domains

Contributors: Hugo Vaysset

What are protein domains ?

Proteins can typically be decomposed into a set of structural or functional units called "domains" where each domain has a specific biological function (e.g. catalyzing a chemical reaction or binding to another protein). The combination of one or several protein domains within a protein determines its biological function.

To examplify this idea, the figure is a depiction of the ThsA protein involved in the Thoeris defense system in Bacillus cereus. The protein is composed of two domains: a SIR2-like domain (blue) and a SLOG domain (green). The SLOG domain of ThsA can bind to cyclic Adenosine Diphosphate Ribose (cADPR), a signalling molecule produced by ThsB upon phage infection. The binding of cADPR activates the Nicotinamide Adenine Dinucleotide (NAD) depletion activity of the SIR2-like domain which causes abortive infection. This shows how the presence of two domains in this protein allows it to be activated by the sensor component of the system (ThsB) and to trigger the immune response mechanism () .

Domain characterization helps to understand the biological function of a protein

Although a considerable diversity of molecular mechanisms have been described for defense systems, it is striking to observe that some functional domains are recurrently involved in antiphage defense () . When studying the presence of a new defense system, the in silico characterization of the domains present in the system can provide valuable information regarding the molecular mechanism of the system. If one protein of the system contains for example a TerB domain, this might indicate that the system is involved in membrane integrity surveillance as this domain was previously shown to be associated with the periplasmic membrane () . If a protein of the system contains a TIR domain this might indicate that the system possesses a NAD degradation activity or that the protein could multimerize as both functions have been shown for this domain in the past () .

Domains can be conserved throughout evolution

It is clear that some defense systems can be conserved among different clades of bacteria but it was also observed that the unit of evolutionary conservation can be the protein domain () . As a consequence, it is frequent to find the same domain associated with a wide range of distinct other domains in different defense systems () . This is well illustrated by defense systems such Avs or CBASS that can be constituted of diverse effector proteins which differ from each other based on the specific domains that compose them () , () , () . The modular aspect of protein domains fits with the concept of "evolution as tinkering" stating that already existing objects (here protein domains) can often be repurposed in new manners, allowing the efficient development of novel functions () .

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