Institut für Virologie, Veterinärmedizin, Freie Universität Berlin, 14163 Berlin, Germany.
Department of Virology, Faculty of Veterinary Medicine, Cairo University, Giza 12613, Egypt.
Int J Mol Sci. 2022 Oct 30;23(21):13209. doi: 10.3390/ijms232113209.
Porcine reproductive and respiratory syndrome virus is a positive-stranded RNA virus of the family . The Gp5/M dimer, the major component of the viral envelope, is required for virus budding and is an antibody target. We used alphafold2, an artificial-intelligence-based system, to predict a credible structure of Gp5/M. The short disulfide-linked ectodomains lie flat on the membrane, with the exception of the erected N-terminal helix of Gp5, which contains the antibody epitopes and a hypervariable region with a changing number of carbohydrates. The core of the dimer consists of six curved and tilted transmembrane helices, and three are from each protein. The third transmembrane regions extend into the cytoplasm as amphiphilic helices containing the acylation sites. The endodomains of Gp5 and M are composed of seven β-strands from each protein, which interact via β-strand seven. The area under the membrane forms an open cavity with a positive surface charge. The M and Orf3a proteins of coronaviruses have a similar structure, suggesting that all four proteins are derived from the same ancestral gene. Orf3a, like Gp5/M, is acylated at membrane-proximal cysteines. The role of Gp5/M during virus replication is discussed, in particular the mechanisms of virus budding and models of antibody-dependent virus neutralization.
猪繁殖与呼吸综合征病毒是正链 RNA 病毒科的一员。病毒包膜的主要成分 Gp5/M 二聚体是病毒出芽所必需的，也是抗体的靶标。我们使用基于人工智能的 AlphaFold2 预测了 Gp5/M 的可信结构。短的二硫键连接的胞外结构域平贴在膜上，除了 Gp5 的竖立的 N 端螺旋，它包含抗体表位和一个具有变化数量碳水化合物的高变区。二聚体的核心由六个弯曲和倾斜的跨膜螺旋组成，其中三个来自每个蛋白。第三个跨膜区作为含有酰化位点的两亲性螺旋延伸到细胞质中。Gp5 和 M 的内结构域由每个蛋白的七个β-链组成，它们通过β-链七相互作用。膜下区域形成一个带有正表面电荷的开放腔。冠状病毒的 M 和 Orf3a 蛋白具有相似的结构，这表明这四种蛋白都来自同一祖先基因。Orf3a 与 Gp5/M 一样，在靠近膜的半胱氨酸处被酰化。讨论了 Gp5/M 在病毒复制过程中的作用，特别是病毒出芽的机制和抗体依赖性病毒中和的模型。
