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.
Kerfelec
Brigitte
B
INRA, UMR1260, Nutriments lipidiques et Prévention des Maladies Métaboliques, Marseille F-13385, France.
Allouche
Maya
M
Colin
Damien
D
Van Eyck
Marie Hélène
MH
Brasseur
Robert
R
Thomas
Annick
A
D000595:Amino Acid Sequence; D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry / Q000378:metabolism*; D003089:Colipases / Q000737:chemistry / Q000378:metabolism*; D019295:Computational Biology; D004795:Enzyme Stability; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008958:Models, Molecular; D008969:Molecular Sequence Data; D013552:Swine
D001647:Bile Acids and Salts; D003089:Colipases; D008055:Lipids; D008823:Micelles