Computational Analysis Reveals a Critical Point Mutation in the N-Terminal Region of the Signaling Lymphocytic Activation Molecule Responsible for the Cross-Species Infection with Canine Distemper Virus.
Computational Analysis Reveals a Critical Point Mutation in the N-Terminal Region of the Signaling Lymphocytic Activation Molecule Responsible for the Cross-Species Infection with Canine Distemper Virus.
复制标题
DOI：
10.3390/molecules26051262
复制
发表时间：
2021-02-26
期刊：
影响因子：
--
通讯作者：
Takeda M
中科院分区：
文献类型：
--
作者：
Yamamoto Y;Nakano S;Seki F;Shigeta Y;Ito S;Tokiwa H;Takeda M
麻疹病毒通过病毒血凝素（H蛋白）和信号淋巴细胞活化分子（SLAM）之间的相互作用促进宿主感染。最近，人SLAM的N-末端区域作为麻疹病毒受体的功能重要性被证明。然而，该区域在其他麻疹病毒感染过程和宿主范围确定中的功能作用仍然未知，部分原因是该区域高度灵活，这阻碍了X射线晶体学对该区域的准确结构测定。本研究利用计算化学方法分析了犬瘟热病毒H蛋白与SLAMs之间的相互作用。分子动力学模拟和片段分子轨道分析表明，猕猴SLAM N端区域独特的His 28是能够与CDV-H形成稳定相互作用的关键决定因素，为猕猴中的CDV感染提供了基础。提出的计算化学方法应该能够确定分子间的相互作用，涉及蛋白质的区域，难以预测的晶体结构，因为它们的高灵活性。
Infection of hosts by morbilliviruses is facilitated by the interaction between viral hemagglutinin (H-protein) and the signaling lymphocytic activation molecule (SLAM). Recently, the functional importance of the n-terminal region of human SLAM as a measles virus receptor was demonstrated. However, the functional roles of this region in the infection process by other morbilliviruses and host range determination remain unknown, partly because this region is highly flexible, which has hampered accurate structure determination of this region by X-ray crystallography. In this study, we analyzed the interaction between the H-protein from canine distemper virus (CDV-H) and SLAMs by a computational chemistry approach. Molecular dynamics simulations and fragment molecular orbital analysis demonstrated that the unique His28 in the N-terminal region of SLAM from Macaca is a key determinant that enables the formation of a stable interaction with CDV-H, providing a basis for CDV infection in Macaca. The computational chemistry approach presented should enable the determination of molecular interactions involving regions of proteins that are difficult to predict from crystal structures because of their high flexibility.
登录
查看更多内容
影响因子：
3.7
作者：
Bieringer M;Han JW;Kendl S;Khosravi M;Plattet P;Schneider-Schaulies J
通讯作者：
Schneider-Schaulies J
影响因子：
16.8
作者：
Hashiguchi, Takao;Ose, Toyoyuki;Yanagi, Yusuke
通讯作者：
Yanagi, Yusuke
影响因子：
5.4
作者：
Seki, F;Ono, N;Yanagi, Y
通讯作者：
Yanagi, Y
影响因子：
5.5
作者：
Roe, Daniel R.;Cheatham, Thomas E., III
通讯作者：
Cheatham, Thomas E., III
影响因子：
2.9
作者：
HOOVER, WG
通讯作者：
HOOVER, WG