Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural insights into autoinhibition and activation of defense-associated sirtuin protein.
Journal, issue, pages	Int J Biol Macromol, Vol. 277, Issue Pt 1, Page 134145, Year 2024
Publish date	Jul 24, 2024
Authors	Xu Yang / Yiqun Wang / Jianting Zheng /
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 ...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.
External links	Int J Biol Macromol / PubMed:39059542
Methods	EM (single particle)
Resolution	2.9 - 9.74 Å
Structure data	39369 EMDB entry, No image 8ykf EMDB-39369, PDB-8ykf: The DSR2-DSAD1 complex with DSAD1 on the opposite sides Method: EM (single particle) / Resolution: 3.35 Å EMDB entry, No image EMDB-39380: Local map of DSR2-DSAD1 complex Method: EM (single particle) / Resolution: 2.9 Å EMDB entry, No image EMDB-39381: Overall map of DSR2-DSAD1 complex Method: EM (single particle) / Resolution: 2.98 Å 39382 EMDB entry, No image 8yl5 EMDB-39382, PDB-8yl5: The DSR2-DSAD1 complex with DSAD1 on the same sides Method: EM (single particle) / Resolution: 3.45 Å 39385 EMDB entry, No image 8yln EMDB-39385, PDB-8yln: The structure of DSR2-Tail tube complex Method: EM (single particle) / Resolution: 3.53 Å EMDB entry, No image EMDB-39386: The loacl refined map of DSR2 and NAD structure Method: EM (single particle) / Resolution: 9.74 Å EMDB entry, No image EMDB-39387: The local refined map of DSR2 N-terminal domains Method: EM (single particle) / Resolution: 2.92 Å 39390 EMDB entry, No image 8ylt EMDB-39390, PDB-8ylt: The structure of DSR2 and NAD+ complex Method: EM (single particle) / Resolution: 3.09 Å 39718 EMDB entry, No image 8z18 EMDB-39718, PDB-8z18: The tetramer complex of DSR2 and tube-forming domain of phage tail tube protein Method: EM (single particle) / Resolution: 3.94 Å 60470 EMDB entry, No image 8ztr EMDB-60470, PDB-8ztr: The dimer complex of DSR2 and tube-forming domain of phage tail tube protein Method: EM (single particle) / Resolution: 3.26 Å
Chemicals	ChemComp-NAD: NICOTINAMIDE-ADENINE-DINUCLEOTIDE / NAD*YM
Source	bacillus subtilis (bacteria) bacillus phage spbeta (virus) bacillus phage spr (virus) bacillus subtilis subsp. natto (strain best195) (bacteria) bacillus subtilis subsp. natto best195 (bacteria)
Keywords	IMMUNE SYSTEM / Complex