Brunelli Roberto, Greco Giulia, Barteri Mario, Krasnowska Ewa K, Mei Giampiero, Natella Fausta, Pala Alessandro, Rotella Simona, Ursini Fulvio, Zichella Lucio, Parasassi Tiziana
Dipartimento di Scienze Ginecologiche, Perinatologia e Puericultura, Università di Roma La Sapienza, Roma, Italy.
FASEB J. 2003 Nov;17(14):2127-9. doi: 10.1096/fj.02-1181fje. Epub 2003 Sep 18.
The major protein component (apoB-100) of low-density lipoprotein (LDL) is known as a multipotential molecule the several functional regions of which can all be affected by key structural modifications driven by specific domains. Based on our previous report on structural and conformational modifications of apoB-100 in the presence of 17-beta-estradiol (E2), we characterized the interaction between E2 and the apoB-100 and further explored the induced alterations in terms of the structural arrangement of the whole LDL particle. We report evidence for the existence on apoB-100 of a single specific and saturable binding site for E2, the occupancy of which modifies the overall structure of the protein, inducing an increase in the alpha-helix fraction. As a consequence, the structure of the LDL particle is deeply perturbed, with a change in the arrangement of both the outer shell and lipid core and an overall volume shrinkage. The evidence of a regulation of apoB-100 structure by a physiological ligand opens new perspectives in the study of the biological addressing of the LDL particle and suggests a novel rationale in the search for mechanisms underlying the beneficial role of E2 in decreasing the risk of early lesions in atherosclerosis.
低密度脂蛋白（LDL）的主要蛋白质成分（载脂蛋白B-100）是一种多潜能分子，其几个功能区域都可能受到特定结构域驱动的关键结构修饰的影响。基于我们之前关于在17-β-雌二醇（E2）存在下载脂蛋白B-100的结构和构象修饰的报告，我们表征了E2与载脂蛋白B-100之间的相互作用，并进一步从整个LDL颗粒的结构排列方面探讨了诱导的变化。我们报告了载脂蛋白B-100上存在一个单一的、特异性的、可饱和的E2结合位点的证据，该位点的占据会改变蛋白质的整体结构，导致α-螺旋比例增加。结果，LDL颗粒的结构受到深度扰动，外壳和脂质核心的排列发生变化，总体积缩小。生理配体对载脂蛋白B-100结构的调节证据为LDL颗粒的生物学靶向研究开辟了新的视角，并为寻找E2降低动脉粥样硬化早期病变风险的有益作用的潜在机制提供了新的理论依据。
