Beijing Advanced Innovation Center for Food Nutrition and Human Health, State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, 100193, China.
Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Beijing, 100093, China.
Nat Commun. 2018 Aug 22;9(1):3373. doi: 10.1038/s41467-018-05619-1.
Honeybee caste development is nutritionally regulated by royal jelly (RJ). Major royal jelly protein 1 (MRJP1), the most abundant glycoprotein among soluble royal jelly proteins, plays pivotal roles in honeybee nutrition and larvae development, and exhibits broad pharmacological activities in humans. However, its structure has long remained unknown. Herein, we identify and report a 16-molecule architecture of native MRJP1 oligomer containing four MRJP1, four apisimin, and eight unanticipated 24-methylenecholesterol molecules at 2.65 Å resolution. MRJP1 has a unique six-bladed β-propeller fold with three disulfide bonds, and it interacts with apisimin mainly by hydrophobic interaction. Every four 24-methylenecholesterol molecules are packaged by two MRJP1 and two apisimin molecules. This assembly dimerizes to form an H-shaped MRJP1-apisimin-24-methylenecholesterol complex via apisimin in a conserved and pH-dependent fashion. Our findings offer a structural basis for understanding the pharmacological effects of MRJPs and 24-methylenecholesterol, and provide insights into their unique physiological roles in bees.
蜂王浆（RJ）调控蜜蜂的品级发育。蜂王浆主要清蛋白 1（MRJP1）是可溶性蜂王浆蛋白中含量最丰富的糖蛋白，在蜜蜂营养和幼虫发育中发挥关键作用，在人类中具有广泛的药理学活性。然而，其结构长期以来一直未知。在此，我们在 2.65Å分辨率下鉴定并报告了一种含有四个 MRJP1、四个apisimin 和八个意想不到的 24-亚甲基胆固醇分子的天然 MRJP1 低聚物的 16 分子结构。MRJP1 具有独特的六叶 β-桨叶折叠结构，有三个二硫键，它主要通过疏水相互作用与 apisimin 相互作用。每四个 24-亚甲基胆固醇分子由两个 MRJP1 和两个 apisimin 分子包装。这种组装通过 apisimin 以保守且依赖 pH 的方式二聚化，形成 H 形的 MRJP1-apisimin-24-亚甲基胆固醇复合物。我们的研究结果为理解 MRJPs 和 24-亚甲基胆固醇的药理学作用提供了结构基础，并为它们在蜜蜂中的独特生理作用提供了新的见解。
