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Publication Abstract from PubMed

The NADase activity of the defense-associated sirtuins (DSRs) is activated by the phage tail tube protein (TTP). Herein, we report cryo-EM structures of a free-state Bacillus subtilis DSR2 tetramer and a fragment of the tetramer, a phage SPR tail tube, and two DSR2-TTP complexes. DSR2 contains an N-terminal SIR2 domain, a middle domain (MID) and a C-terminal domain (CTD). The DSR2 CTD harbors the alpha-solenoid tandem-repeats like the HEAT-repeat proteins. DSR2 assembles into a tetramer with four SIR2 clustered at the center, and two intertwined MID-CTD chains flank the SIR2 core. SPR TTPs self-assemble into a tube-like complex. Upon DSR2 binding, the D1 domain of SPR TTP is captured between the HEAT-repeats domains of DSR2, which conflicts with TTPs self-assembly. Binding of TTPs induces conformational changes in DSR2 tetramer, resulting in increase of the NAD(+) pocket volume in SIR2, thus activates the NADase activity and leads to cellular NAD(+) depletion.

Activation of the bacterial defense-associated sirtuin system.,Zhu K, Shang K, Wang L, Yu X, Hua L, Zhang W, Qin B, Wang J, Gao X, Zhu H, Cui S Commun Biol. 2025 Feb 24;8(1):297. doi: 10.1038/s42003-025-07743-3. PMID:39994439^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.