The C-terminal end of PLIN1 displays structural disorder.

Lipid droplets (LDs) serve as crucial organelles for lipid storage and metabolism, with their proteome significantly influencing their regulation. Perilipins (PLINs), in particular PLIN1, play vital role in LD metabolism by orchestrating lipolysis. The C-terminal end of PLIN1 regulates lipolysis through interactions with coactivators such as the CGI-58 protein. Despite its importance, the structural characterization of this domain remains limited. Here, we present a comprehensive bioinformatic and biophysical analysis of the C-terminal end of mouse PLIN1 (mPLIN1C). Our findings suggest that mPLIN1C behaves as an intrinsically disordered region (IDR), exhibiting context-dependent properties of the coil-like or pre-molten globule type. Structural analysis reveals a predominance of disordered secondary structure, with circular dichroism spectroscopy indicating a high coil content. Interaction studies with SDS micelles suggest a conformational transition towards a pre-molten globule state. Furthermore, the analysis of molecular recognition features (MoRFs) identifies the EPESE sequence spanning residues 413-417 as a potential binding site for partner molecules. Overall, our findings shed light on the structural properties and potential interaction mechanisms of mPLIN1C, providing insight into its functional role in LD metabolism.