The structure of NAD⁺ consuming protein Acinetobacter baumannii TIR domain shows unique kinetics and conformations.

ABSTRACT: Toll-like and interleukin-1/18 receptor/resistance (TIR) domain-containing proteins function as important signaling and immune regulatory molecules. TIR domain-containing proteins identified in eukaryotic and prokaryotic species also exhibit NAD+ hydrolase activity in select bacteria, plants, and mammalian cells. We report the crystal structure of the Acinetobacter baumannii TIR domain protein (AbTir-TIR) with confirmed NAD⁺ hydrolysis and map the conformational effects of its interaction with NAD⁺ using hydrogen-deuterium exchange-mass spectrometry. NAD⁺ results in mild decreases in deuterium uptake at the dimeric interface. In addition, AbTir-TIR exhibits EX1 kinetics indicative of large cooperative conformational changes, which are slowed down upon subst

SUBMITTER: Klontz E 

PROVIDER: S-EPMC10641520 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature