Chemical-Shift Perturbations Reflect Bile Acid Binding to Norovirus Coat Protein: Recognition Comes in Different Flavors
Chemical-Shift Perturbations Reflect Bile Acid Binding to Norovirus Coat Protein: Recognition Comes in Different Flavors
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DOI：
10.1002/cbic.201900572
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发表时间：
2019-12-05
期刊：
影响因子：
3.2
通讯作者：
Mallagaray, Alvaro
中科院分区：
文献类型：
--
作者：
Creutznacher, Robert;Schulze, Eric;Mallagaray, Alvaro
据报道，胆汁酸是促进细胞培养物中人和鼠诺如病毒（NoV）感染的重要辅因子。根本机制尚未解决。通过使用化学位移扰动（CSP）NMR实验，我们确定了一个低亲和力的胆汁酸结合位点的人GII.4 NoV菌株。长时间尺度的MD模拟揭示了一个灵活的形状配体可访问的结合口袋的形成，允许形成稳定的病毒外壳蛋白-胆汁酸复合物与实验CSP数据一致。CSP NMR实验还表明，胆汁酸结合的这种模式对组织-血型抗原的结合有微小的影响，反之亦然。探测胆汁酸与七种不同菌株的病毒样颗粒结合的STD NMR实验表明，低亲和力胆汁酸结合是人NoV的共同特征，因此对于理解胆汁酸作为辅因子在NoV感染中的作用应该是重要的。
Bile acids have been reported as important cofactors promoting human and murine norovirus (NoV) infections in cell culture. The underlying mechanisms are not resolved. Through the use of chemical shift perturbation (CSP) NMR experiments, we identified a low-affinity bile acid binding site of a human GII.4 NoV strain. Long-timescale MD simulations reveal the formation of a ligand-accessible binding pocket of flexible shape, allowing the formation of stable viral coat protein-bile acid complexes in agreement with experimental CSP data. CSP NMR experiments also show that this mode of bile acid binding has a minor influence on the binding of histo-blood group antigens and vice versa. STD NMR experiments probing the binding of bile acids to virus-like particles of seven different strains suggest that low-affinity bile acid binding is a common feature of human NoV and should therefore be important for understanding the role of bile acids as cofactors in NoV infection.