Interactions of Leptospiral PI-PLC with the membrane phosphoinositides: an insight of the proteinphospholipid association in the pathogenesis

Abstract

Protein-phospholipid interactions encompass the basis of many biological processes, including host-pathogen interaction and disease progression. This study reports the interactions of Leptospiral PI-PLC (LA_1375) with PIP2 and PIP3. Molecular docking analysis was carried out to unveil the interactions of the protein with the plasma membrane phosphoinositides. The binding affinities of the interactions, most favourable protein-phospholipid binding poses, and the binding site residues were revealed. The binding energies were found to be -14.04 and -11.64 kcal/mol respectively for PIP2 and PIP3 interaction. Also, the analysis explored the high-affinity binding of the protein with the substrate PIP2. PIP2 is the precursor of intracellular second messengers DAG and IP3; responsible for the activation of pro-inflammatory mediators and other signalling events. Moreover, both PIP2 and PIP3 have been implicated in various cellular processes through the activation of lipid signalling cascades. Hence, further in-vitro confirmation of the annotated interactions may open up new dimensions in the pathogenesis of Leptospirosis.