Does intrinsic disorder in proteins favors their interaction with lipids?

Intrinsically disordered proteins (IDPs) are implicated in a range of human diseases, some of which are associated with ability of certain IDPs to bind lipids. Although the presence of solvent-exposed hydrophobic regions in IDPs should favor their interactions with low-molecular-weight hydrophobic/amphiphilic compounds, this hypothesis has not been systematically explored as of yet. In this study, analysis of the DisProt database with regard to the presence of lipid-binding IDPs (LBIDPs) reveals that they comprise at least 15% of DisProt entries. LBIDPs are classified into four groups by ligand type, functional categories, domain structure, and conformational state. 57% of LBIDPs are classified as ordered according to CH-CDF analysis, and 70% of LBIDPs possess length of disordered regions below 50%. To investigate lipid-binding properties of IDPs, for which lipid binding was not reported, we have rationally selected three proteins from different conformational groups. They all are shown to bind linoleic (LA) and oleic (OA) acids with the capacities ranging from 9 to 34 LA/OA molecules per protein molecule. The association with LA/OA causes formation of the high-molecular-weight lipid-protein complexes. These findings suggest that lipid binding is common among IDPs, which could favor their involvement into lipid metabolism. This article is protected by copyright. All rights reserved.