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

A DALI search for structural similarity reveals no close homolog to nsp4C in the Protein Data Bank, indicating this structure should have a new fold ( Fig. 2A and 2B) . The refined WT model contains two nsp4C molecules in one asymmetric unit, termed A and B respectively. The structures of molecule A and B are generally similar with a root mean square deviation (r.m.s.d.) between equivalent Ca atoms of 0.47 Ã… , although there was a notable lack of electron density for residues S489-Q496 in molecule A and residues S493-Q496 in molecule B. From the crystal packing of WT dimer shown in Fig. 3D , it is evident that C-terminal of molecule B in the dimer (colored in magenta) intersects with the Cterminal of another symmetry-related molecule (colored in blue); the same interaction is not observed in the C-terminal of molecule A. Thus, the interaction with symmetry-related molecules at the C-terminal of molecule B helps to stabilize its conformation and results in detectable electron density from S489-T492. The lack of this interaction in molecule A results in its flexibility and undetectable electron density from S489-Q496.