Crystal Structure of the C-Terminal Cytoplasmic Domain of Non-Structural Protein 4 from Mouse Hepatitis Virus A59

Xu, Xiaoling; Lou, Zhiyong; Ma, Yanlin; Chen, Xuehui; Yang, Zhangsheng; Tong, Xiaohang; Zhao, Qi; Xu, Yuanyuan; Deng, Hongyu; Bartlam, Mark; Rao, Zihe

Thus, the mutant C425S monomer structure contains four ahelices (a1-a4) and four b-strands (b1-b4). The conformation of the four a-helices and b-strands b1-b2 are identical to WT, while a short b-strand (b3, S449-M452) between a3 and a4 and a long b-strand b4 (b4, T487-S493) at the C-terminal are formed for stability of the dimer during the crystal packing. The electrostatic surface potential of the mutant monomer is similar to WT nsp4C but with the addition of an extended hydrophobic surface formed by the elongated C-terminal, the hydrophobic cavity is similar in both the WT and C425S mutant structures, and the Ala488-Leu495 (b4) and Ser450-Met452 (b3) loops are critical in forming the hole in the surface of mutant monomer (Fig. 3C) . It is also likely that the C-terminal is essential for stability both in the WT nsp4C and C425S mutant, since the expression of a DF484-Q496 deletion mutant has very low yield compared to the WT nsp4C protein.