Crystal Structure of Fungal Nonspecific Phospholipase C Unveils a Distinct Catalytic Mechanism

Nonspecific phospholipase C (NPC) plays a pivotal role in hydrolyzing phospholipids, releasing diacylglycerol-an essential second messenger. Extensive research has elucidated the structure and function of bacterial and plant NPCs, but our understanding of their fungal counterparts remains limited. Here, we present the first crystal structure of a fungal NPC derived from Rasamsonia emersonii (RePLC), unraveling its distinguishable features divergent from other known phospholipase C. Remarkably, the structure of RePLC contains solely the phosphoesterase domain without the crucial C-terminal domain (CTD) found in plant NPCs, although CTD is important for their activity. Through a comparative analysis of structural features among NPCs from diverse species combined with structure-based mutation analyses and bioinformatics methods, we propose a potential molecular mechanism that may universally underlie the catalysis of phospholipid hydrolysis in fungal NPCs. Furthermore, our study sheds light on the captivating evolutionary trajectory of enzymes across diverse species.

Automated summary

This study presents the crystal structure of a fungal NPC derived from Rasamsonia emersonii, revealing its distinguishable features from other known phospholipase C. The structure of the fungal NPC lacks the C-terminal domain (CTD) found in plant NPCs, which is crucial for their activity. Through comparative analysis and mutation studies, a potential molecular mechanism underlying phospholipid hydrolysis in fungal NPCs is proposed. Furthermore, the study sheds light on the evolutionary trajectory of enzymes across diverse species.