Diamond Light Source (United Kingdom), Harwell Science and Innovation Campus, Didcot OX110DE, UK.
Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Oxford OX37BN, UK.
Viruses. 2023 Jun 23;15(7):1424. doi: 10.3390/v15071424.
CD46, or membrane cofactor protein, is a type-one transmembrane protein from the complement regulatory protein family. Alongside its role in complement activation, CD46 is involved in many other processes, from T-cell activation to reproduction. It is also referred to as a pathogen magnet, because it is used as a receptor by multiple bacteria and viruses. Bovine CD46 (bovCD46) in particular is involved in bovine viral diarrhoea virus entry, an economically important disease in cattle industries. This study presents the X-ray crystallographic structure of the extracellular region of bovCD46, revealing a four-short-consensus-repeat (SCR) structure similar to that in human CD46. SCR1-3 are arranged linearly, while SCR 4 has a reduced interface angle, resulting in a hockey stick-like appearance. The structure also reveals the bovine viral diarrhoea virus interaction site in SCR1, which is likely to confer pestivirus specificity for their target host, CD46. Insights gained from the structural information on pestivirus receptors, such as CD46, could offer valuable guidance for future control strategies.
CD46，也称为膜辅因子蛋白，是补体调控蛋白家族中的一种 I 型跨膜蛋白。除了在补体激活中的作用外，CD46 还参与许多其他过程，从 T 细胞激活到生殖。它也被称为病原体磁铁，因为它被多种细菌和病毒用作受体。特别是牛 CD46（bovCD46）参与牛病毒性腹泻病毒的进入，这是牛产业中一种具有经济重要性的疾病。本研究展示了牛 CD46 胞外区的 X 射线晶体结构，揭示了类似于人 CD46 的四短共识重复（SCR）结构。SCR1-3 线性排列，而 SCR4 的界面角度减小，呈现出曲棍球棒状外观。该结构还揭示了 SCR1 中牛病毒性腹泻病毒的相互作用位点，这可能赋予了瘟病毒对其靶宿主 CD46 的特异性。从 CD46 等瘟病毒受体的结构信息中获得的见解，可能为未来的控制策略提供有价值的指导。
