Páez-Pérez Edgar D, Llamas-García Miriam Livier, Montero-Morán Gabriela M, Lara-González Samuel
IPICYT, Instituto Potosino de Investigación Científica y Tecnológica A.C., División de Biología Molecular, S.L.P, 78216, San Luis Potosí, Mexico.
Universidad Autónoma de San Luis Potosí, Facultad de Ciencias Químicas, S.L.P., 78216, San Luis Potosí, Mexico.
Biochem Biophys Rep. 2025 Feb 28;42:101963. doi: 10.1016/j.bbrep.2025.101963. eCollection 2025 Jun.
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.
脂滴（LDs）是脂质储存和代谢的关键细胞器，其蛋白质组对其调节有显著影响。周脂素（PLINs），尤其是PLIN1，通过协调脂解作用在脂滴代谢中发挥重要作用。PLIN1的C末端通过与共激活因子如CGI-58蛋白相互作用来调节脂解作用。尽管其很重要，但该结构域的结构表征仍然有限。在这里，我们对小鼠PLIN1（mPLIN1C）的C末端进行了全面的生物信息学和生物物理分析。我们的研究结果表明，mPLIN1C表现为一个内在无序区域（IDR），呈现出类似卷曲或预熔球状体类型的上下文依赖特性。结构分析揭示了无序二级结构占主导，圆二色光谱表明高卷曲含量。与SDS胶束的相互作用研究表明向预熔球状体状态发生构象转变。此外，对分子识别特征（MoRFs）的分析确定了跨越413 - 417位残基 的EPESE序列作为伴侣分子的潜在结合位点。总体而言，我们的研究结果揭示了mPLIN1C的结构特性和潜在的相互作用机制，为其在脂滴代谢中的功能作用提供了见解。
