Predicted structural mimicry of spike receptor-binding motifs from highly pathogenic human coronaviruses.
Predicted structural mimicry of spike receptor-binding motifs from highly pathogenic human coronaviruses.
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DOI：
10.1016/j.csbj.2021.06.041
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发表时间：
2021
影响因子：
6
通讯作者：
Blundell TL
中科院分区：
文献类型：
--
作者：
Beaudoin CA;Jamasb AR;Alsulami AF;Copoiu L;van Tonder AJ;Hala S;Bannerman BP;Thomas SE;Vedithi SC;Torres PHM;Blundell TL
结构比较揭示冠状病毒刺突蛋白的潜在拟态。确定了人类和非人类蛋白质与病毒的潜在相互作用。蛋白质-蛋白质对接证实了预测的结构模拟。基于表位的比对可能有助于指导疫苗工作。病毒经常编码模仿宿主蛋白质的蛋白质，以促进感染。关于SARS-CoV-2、SARS-CoV和MERS-CoV刺突蛋白的潜在拟态，特别是受体结合基序的研究很少，而受体结合基序对于确定病毒的趋向性和可药物性可能很重要。利用序列同源性方法在冠状病毒刺突蛋白上检测到肽基和表位基序；然而，比较蛋白质的三维形状已被证明在预测模仿方面比基于序列的比较更有信息。在这里，我们使用结构生物信息学软件来表征三种冠状病毒刺突蛋白受体结合基序的潜在拟态。我们利用序列无关的比对工具来比较结构上已知的蛋白质模型与受体结合基序，并通过蛋白质对接模拟验证潜在的模拟相互作用。所有三种受体结合基序都返回了人类和非人类蛋白。例如，这三种蛋白都与几种含有egf样结构域的蛋白相似：其中一些是人类内源性的，如血栓调节蛋白，另一些是外源性的，如恶性疟原虫MSP-1。与人类蛋白质的相似性可能揭示了刺突蛋白选择的途径，而类似的非人类蛋白质可能表明共享的宿主相互作用伙伴和重叠的抗体交叉反应性。这些发现可以帮助指导实验工作，以进一步了解人类和冠状病毒蛋白质之间的潜在相互作用。
Potential coronavirus spike protein mimicry revealed by structural comparison. Human and non-human protein potential interactions with virus identified. Predicted structural mimicry corroborated by protein–protein docking. Epitope-based alignments may help guide vaccine efforts. Viruses often encode proteins that mimic host proteins in order to facilitate infection. Little work has been done to understand the potential mimicry of the SARS-CoV-2, SARS-CoV, and MERS-CoV spike proteins, particularly the receptor-binding motifs, which could be important in determining tropism and druggability of the virus. Peptide and epitope motifs have been detected on coronavirus spike proteins using sequence homology approaches; however, comparing the three-dimensional shape of the protein has been shown as more informative in predicting mimicry than sequence-based comparisons. Here, we use structural bioinformatics software to characterize potential mimicry of the three coronavirus spike protein receptor-binding motifs. We utilize sequence-independent alignment tools to compare structurally known protein models with the receptor-binding motifs and verify potential mimicked interactions with protein docking simulations. Both human and non-human proteins were returned for all three receptor-binding motifs. For example, all three were similar to several proteins containing EGF-like domains: some of which are endogenous to humans, such as thrombomodulin, and others exogenous, such as Plasmodium falciparum MSP-1. Similarity to human proteins may reveal which pathways the spike protein is co-opting, while analogous non-human proteins may indicate shared host interaction partners and overlapping antibody cross-reactivity. These findings can help guide experimental efforts to further understand potential interactions between human and coronavirus proteins.
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影响因子：
64.5
作者：
ALCAMI, A;SMITH, GL
通讯作者：
SMITH, GL
影响因子：
5.7
作者：
Bowden, Thomas A.;Aricescu, A. Radu;Jones, E. Yvonne
通讯作者：
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影响因子：
3.7
作者：
Ayoub, Ronald;Lee, Yugyung
通讯作者：
Lee, Yugyung
影响因子：
2
作者：
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通讯作者：
Miyara, Makoto
影响因子：
4
作者：
Bautista-Vargas, Mario;Bonilla-Abadia, Fabio;Canas, Carlos A.
通讯作者：
Canas, Carlos A.