Glycans modulate lipid binding in Lili-Mip lipocalin protein: insights from molecular simulations and protein network analyses.

This article focuses on the molecular dynamics and functional role of glycosylation in Lili-Mip, a lipid-binding glycoprotein found in the viviparous Pacific beetle cockroach (Diploptera punctata) that provides nutrition to embryos. Using all-atom molecular dynamics simulations of various glycosylated and deglycosylated states, the study reveals that glycans induce localized conformational fluctuations that regulate the opening-closing motions of the lipid-binding portal and preserve the native, solvent-exposed orientation of the bound oleic acid ligand. Glycosylation also allosterically modulates the β-barrel architecture of Lili-Mip, influencing ligand binding specificity and dynamics, while network analyses identify key residues whose interactions are stabilized by glycans to maintain protein structural integrity during lipid binding. The findings suggest that glycans have functional roles beyond nutrition, potentially facilitating ligand recruitment and release, and that glycosylation likely precedes lipid binding to optimize protein dynamics and ligand availability.