PDF(Pubmed)
Abstract：
Parvovirus B19 (B19V) is a human pathogen that is the causative agent of several diseases in infants and adults. Due to a lack of antivirals against this virus, treatment options are limited. The minor capsid protein of B19V has a unique N terminus, named VP1u, which is essential for infection. The VP1u encodes a receptor binding domain (RBD), necessary for host cell entry, and a phospholipase A2 (PLA2) domain, crucial for endosomal escape during cellular trafficking. Both domains are indispensable for infection, making the RBD a plausible drug target for inhibitors against B19V, as it is located on the exterior surface of the virus. To date, no experimental structural information has been available for the VP1u component for any Parvovirus. Here we report the backbone NMR resonance assignments for the RBD of B19V and demonstrate it forms a stable structure. The backbone chemical shifts are in good agreement with a structure predicted by AlphaFold, validating that the RBD contains three helices connected by tight turns. This RBD construct can now be used for further NMR studies, including assignment of full-length VP1u, determination of protein-protein interaction interfaces, and development of B19 antivirals specific to the RBD domain. Database: BMRB submission code: 52440.
摘要：
细小病毒B19（B19V）是一种人类病原体，是婴儿和成人几种疾病的病原体。由于缺乏针对这种病毒的抗病毒药物，治疗方案有限。B19V的次要衣壳蛋白具有独特的N末端，命名为VP1u，这对感染至关重要。VP1u编码受体结合域（RBD），宿主细胞进入所必需的，和磷脂酶A2（PLA2）结构域，对于细胞运输过程中的内体逃逸至关重要。这两个领域都是感染不可或缺的，使RBD成为B19V抑制剂的合理药物靶标，因为它位于病毒的外表面。迄今为止,没有任何细小病毒的VP1u组件的实验性结构信息。在这里，我们报告了B19V的RBD的主链NMR共振分配，并证明了它形成了稳定的结构。主链化学位移与AlphaFold预测的结构非常吻合，验证RBD包含通过紧密转弯连接的三个螺旋。这种RBD构建体现在可以用于进一步的NMR研究，包括全长VP1u的赋值，蛋白质-蛋白质相互作用界面的测定，以及RBD域特异性B19抗病毒药物的开发。数据库:BMRB提交代码:52440。
