Computational Study Of Colipase Interaction With Lipid Droplets And Bile Salt Micelles

Colipase is a key element in the lipase-catalyzed hydrolysis of dietary lipids.
Although devoid of enzymatic activity, colipase promotes the pancreatic lipase
activity in physiological intestinal conditions by anchoring the enzyme at the
surface of lipid droplets. Analysis of structures of NMR colipase models and
simulations of their interactions with various lipid aggregates, lipid droplet,
and bile salt micelle, were carried out to determine and to map the lipid binding
sites on colipase. We show that the micelle and the oil droplet bind to the same
side of colipase 3D structure, mainly the hydrophobic fingers. Moreover, it
appears that, although colipase has a single direction of interaction with a
lipid interface, it does not bind in a specific way but rather oscillates between
different positions. Indeed, different NMR models of colipase insert different
fragments of sequence in the interface, either simultaneously or independently.
This supports the idea that colipase finger plasticity may be crucial to adapt
the lipase activity to different lipid aggregates.