Montserrat-Canals Mateu, Schnelle Kilian, Leipart Vilde, Halskau Øyvind, Amdam Gro V, Moeller Arne, Cunha Eva S, Luecke Hartmut
Department of Chemistry, University of Oslo, Oslo, Norway.
Norwegian Centre for Molecular Medicine, University of Oslo, Oslo, Norway.
Nat Commun. 2025 Jul 1;16(1):5736. doi: 10.1038/s41467-025-58575-y.
Vitellogenin (Vg) is the main yolk precursor lipoprotein in almost all egg-laying animals. In addition, along its evolutionary history, Vg has developed a range of new functions in different taxa. In the honey bee, Vg has functions related to immunity, antioxidant protection, social behavior and longevity. However, the molecular mechanisms underlying Vg functionalities are still poorly understood. Here, we report the cryo-EM structure of full-length honey bee Vg, one-step purified directly from hemolymph. The structure provides structural insights into the overall domain architecture, including the lipid binding cavity and the previously uncharacterized von Willebrand factor type D domain. A domain of unknown function has been identified as a C-terminal cystine knot domain based on structural homology. Information about post-translational modifications, cleavage products, metal and lipid binding allow an improved understanding of the mechanisms underlying the range of Vg functionalities. The findings have numerous implications for the structure-function relationship of vitellogenins of other species as well as members of the same protein superfamily, which share the same structural elements.
卵黄原蛋白（Vg）是几乎所有产卵动物中主要的卵黄前体脂蛋白。此外，在其进化历程中，Vg在不同分类群中发展出了一系列新功能。在蜜蜂中，Vg具有与免疫、抗氧化保护、社会行为和寿命相关的功能。然而，Vg功能的分子机制仍知之甚少。在此，我们报道了直接从血淋巴中一步纯化得到的全长蜜蜂Vg的冷冻电镜结构。该结构为整体结构域架构提供了结构见解，包括脂质结合腔和先前未表征的冯·威勒布兰德因子D型结构域。基于结构同源性，一个功能未知的结构域被鉴定为C端胱氨酸结结构域。有关翻译后修饰、裂解产物、金属和脂质结合的信息有助于更好地理解Vg功能范围背后的机制。这些发现对其他物种的卵黄原蛋白以及具有相同结构元件的同一蛋白质超家族成员的结构-功能关系具有诸多启示。
