8Z18

The tetramer complex of DSR2 and tube-forming domain of phage tail tube protein

Summary for 8Z18

• Entry DOI: 10.2210/pdb8z18/pdb
• EMDB information: 39718
• Descriptor: SIR2-like domain-containing protein, Bacillus phage SPR Tube protein (2 entities in total)
• Functional Keywords: complex, immune system
• Biological source: Bacillus subtilis subsp. natto (strain BEST195); More
• Total number of polymer chains: 8
• Total formula weight: 591761.96

Authors

Zheng, J.,Yang, X. (deposition date: 2024-04-10, release date: 2024-08-14)

Primary citation

Yang, X.,Wang, Y.,Zheng, J.
Structural insights into autoinhibition and activation of defense-associated sirtuin protein.
Int.J.Biol.Macromol., 277:134145-134145, 2024

PubMed Abstract: Bacterial defense-associated sirtuin 2 (DSR2) proteins harbor an N-terminal sirtuin (SIR2) domain degrading NAD. DSR2 from Bacillus subtilis 29R is autoinhibited and unable to hydrolyze NAD in the absence of phage infection. A tail tube protein (TTP) of phage SPR activates the DSR2 while a DSR2-inhibiting protein of phage SPbeta, known as DSAD1 (DSR anti-defense 1), inactivates the DSR2. Although DSR2 structures in complexed with TTP and DSAD1, respectively, have been reported recently, the autoinhibition and activation mechanisms remain incompletely understood. Here, we present cryo-electron microscopy structures of the DSR2-NAD complex in autoinhibited state and the in vitro assembled DSR2-TFD (TTP tube-forming domain) complex in activated state. The DSR2-NAD complex reveals that the autoinhibited DSR2 assembles into an inactive tetramer, binding NAD through a distinct pocket situated outside active site. Binding of TFD into cavities within the sensor domains of DSR2 triggers a conformational change in SIR2 regions, activating its NADase activity, whereas the TTP β-sandwich domain (BSD) is flexible and does not contribute to the activation process. The activated form of DSR2 exists as tetramers and dimers, with the tetramers exhibiting more NADase activity. Overall, our results extend the current understanding of autoinhibition and activation of DSR2 immune proteins.

PubMed: 39059542
DOI: 10.1016/j.ijbiomac.2024.134145

Experimental method

ELECTRON MICROSCOPY (3.94 Å)