Does Intrinsic Disorder in Proteins Favor Their Interaction with Lipids?

Abstract

Intrinsically disordered proteins (IDPs) are implicated in a range of human diseases, some of which are associated with the ability to bind to 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, the 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 the CH‐CDF analysis, and 70% of LBIDPs possess lengths of disordered regions below 50%. To investigate the lipid‐binding properties of IDPs for which lipid binding is not reported, three proteins from different conformational groups are rationally selected. They all are shown to bind linoleic (LA) and oleic (OA) acids with capacities ranging from 9 to 34 LA/OA molecules per protein molecule. The association with LA/OA causes the formation of high‐molecular‐weight lipid–protein complexes. These findings suggest that lipid binding is common among IDPs, which can favor their involvement in lipid metabolism.

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“…The authors also experimentally analyzed the oleic/linoleic acid binding capability of several DisProt entries with different levels/degrees of disorder, for which no information on ability to bind lipids was reported. All these IDPs were able to bind lipids, and their OA/LA binding capacities were positively correlated with the extent of disorder . These observations suggest the ability to bind lipids and other low‐molecular‐weight hydrophobic and amphiphilic substances might represent a general property of IDPs/IDPRs …”

“…All these IDPs were able to bind lipids, and their OA/LA binding capacities were positively correlated with the extent of disorder . These observations suggest the ability to bind lipids and other low‐molecular‐weight hydrophobic and amphiphilic substances might represent a general property of IDPs/IDPRs …”

“…All these IDPs were able to bind lipids, and their OA/LA binding capacities were positively correlated with the extent of disorder. [17] These observations suggest the ability to bind lipids and other low-molecular-weight hydrophobic and amphiphilic substances might represent a general property of IDPs/IDPRs. [17] Finally, we present a viewpoint article, where we place an argument that the time is right for establishing a set of standardbased guidelines to evaluate, interpret, and report computational protein disorder predictions.…”

“…This finding provided a mechanistic explanation for the ability of some amyloidogenic sequence to fold in either the ring-like shape oligomers or elongated amyloid fibrils. [16] Deryusheva et al [17] conducted an analysis of the DisProt database (http://www.disprot.org/), [18] to evaluate the prevalence of lipid-binding IDPs (LBIDPs). This analysis showed that at least 15% of experimentally validated IDPs are able to bind lipids, and these LBIDPs were grouped into four classes based on their conformational state, domain structure, functional categories, and ligand type.…”

“…Deryusheva et al . conducted an analysis of the DisProt database (http://www.disprot.org/), to evaluate the prevalence of lipid‐binding IDPs (LBIDPs).…”