Structure of the divergent human astrovirus MLB capsid spike.
Structure of the divergent human astrovirus MLB capsid spike.
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DOI：
10.1016/j.str.2022.10.010
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发表时间：
2022-12-01
期刊：
影响因子：
5.7
通讯作者：
DuBois, Rebecca M.
中科院分区：
文献类型：
--
作者：
Delgado-Cunningham, Kevin;Lopez, Tomas;Khatib, Firas;Arias, Carlos F.;DuBois, Rebecca M.
尽管它们在世界范围内流行并与人类疾病相关，但人类星状病毒（HAstV）感染和进化的分子基础仍然缺乏特征。在这里，我们报道了发散型hslb分支（HAstV MLB）的衣壳蛋白穗的结构。虽然这种结构与经典进化支的HAstV尖峰具有相似的折叠拓扑结构，但在其他方面却截然不同。我们没有发现MLB和经典的HAstV刺突之间存在保守的受体结合位点的证据，这表明MLB和经典的HAstV利用不同的受体来附着宿主细胞。我们使用一种新的HAstV感染竞争试验为这一假设提供了证据。将HAstV MLB的扣球结构与其序列预测的结构进行比较，结果显示匹配不佳，但相对于基于机器学习的预测，基于模板的预测令人惊讶地准确。我们的数据为理解多种hastv的感染机制提供了基础，并可以支持在类似的未研究系统中确定结构。Delgado-Cunningham等人报道了人类星状病毒MLB1株衣壳刺突的结构。衣壳刺突在病毒表面形成突起，可能在附着在人体细胞上起作用。MLB1的刺突结构与经典人类星状病毒的刺突结构有许多不同。
Despite their worldwide prevalence and association with human disease, the molecular bases of human astrovirus (HAstV) infection and evolution remain poorly characterized. Here, we report the structure of the capsid protein spike of the divergent HAstV MLB-clade (HAstV MLB). While the structure shares a similar folding topology with that of classical-clade HAstV spikes, it is otherwise strikingly different. We find no evidence of a conserved receptor-binding site between the MLB and classical HAstV spikes, suggesting that MLB and classical HAstVs utilize different receptors for host cell attachment. We provide evidence for this hypothesis using a novel HAstV infection competition assay. Comparisons of the HAstV MLB spike structure to structures predicted from its sequence reveal poor matches, but template-based predictions were surprisingly accurate relative to machine-learning-based predictions. Our data provide a foundation for understanding the mechanisms of infection by diverse HAstVs and can support structure determination in similarly unstudied systems. Delgado-Cunningham et al. report the structure of the capsid spike from human astrovirus strain MLB1. The capsid spike forms protrusions on the surface of the virus and may have a role in attaching to human cells. The MLB1 spike structure has many differences compared to classical human astrovirus spike structures.
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