Computational Insight into Parasite Lipid Binding Proteins–Membrane Interactions

FERNANDO ZAMARREÑO; JUAN FRANCISCO VISO; DIEGO OBIOL; MARCELO D. COSTABEL

Córdoba

Congreso; LI Reunión Anual de la Sociedad Argentina de Biofísica; 2023

Sociedad Argentina de Biofísica

Parasitic infections pose a significant global health threat, necessitating a comprehensiveunderstanding of the molecular mechanisms employed by parasites for survival withintheir hosts. This study focuses on Lipid-Binding Proteins (LBPs) derived from helminths,which play a crucial role in the acquisition and utilization of essential lipids from the host.The structural diversity of these LBPs, including the Nematode Polyprotein Allergens(NPAs), Fatty Acid and Retinol-binding proteins (FARs), and Schistosoma japonicum FattyAcid-Binding Protein (Sj-FABPc), underscores the complexity of their interactions with hostcells and membranes. Leveraging methodologies used in previous studies, we studied thelipid transport properties through protein-membrane electrostatic interactions.To achieve this goal, we employed computational analyses to model helminth LBPs -cellular membranes interactions. Our computational framework, utilizing the FiniteDifference Poisson Boltzmann Equation (FDPB) and the self-developed software Aquilles,allowed us to quantify the electrostatic energy involved in these interactions, discerningamong potential membrane-bound mechanisms.In particular, we sought to understand whether the helminth LBPs exhibit distinctmechanisms in transferring fatty acid ligands to phospholipid membranes. In accordancewith in vitro studies, our work confirms that Sj-FABPc utilizes a collisional mechanism,while Ov-FAR-1 and NPA proteins transfer ligands via aqueous diffusion. Building uponthe proposed classification of collisional and diffusional mechanisms for FABPs, weextended our analysis to identify crucial residues, showcasing how punctual mutationsinfluence the interaction of these proteins with membranes. This investigation, supportedby bioinformatics and electrostatic energy calculations, not only elucidates the diversemembrane interactions of helminth LBPs but also sets the groundwork for future studieson related lipid-binding proteins.