Unveiling the structural arrangement of the multidomain flavodiiron protein from the human pathogen Clostridioides difficile, a key protein

SOS CryoEM Understand how pathogenic bacteria suppress the defense barriers imposed by the immune system in humans is of major relevance. Thus it is urgent to study the mechanisms against NO generated by macrophages, or O2 and reactive oxygen species. A key enzyme in the ROS detoxification is the flavodiiron protein, FDP, constituted by a minimal core unit: metallo-β-lactamase-like, and flavodoxin domains. The FDP Class F, from the human pathogen Clostridioides difficile, contains additional redox domains and is proposed to play a crucial role as a protection mechanism. We aim to determine by Cryo-EM Single Particle Analysis the structure of the C. difficile FDP. At the current moment, there is no structural information for the more complex FDPs, and therefore this proposal represents a breakthrough in this field. Study the structural determinants of these extra domains is essential to understand their role in these FDPs and, most importantly, their role in the infection process.