Crystal Structure of the Oligomerization Domain of NSP4 from Rotavirus Reveals a Core Metal-binding Site

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• 作者：Bowman ; Gregory D. ; Nodelman ; Ilana M. ; Levy ; Orlie ; Lin ; Shuo L. ; Tian ; Peng ; Zamb ; Timothy J. ; et. al.
• 刊名：Journal of Molecular Biology
• 出版年：2000
• 出版时间：December 15, 2000
• 年：2000
• 卷：304
• 期：5
• 页码：861-871
• 全文大小：475 K

文摘

During the maturation of rotaviral particles, non-structural protein 4 (NSP4) plays a critical role in the translocation of the immature capsid into the lumen of the endoplasmic reticulum. Full-length NSP4 and a 22 amino acid peptide (NSP4_114-135) derived from this protein have been shown to induce diarrhea in young mice in an age-dependent manner, and may therefore be the agent responsible for rotavirally-induced symptoms. We have determined the crystal structure of the oligomerization domain of NSP4 which spans residues 95 to 137 (NSP4_95-137). NSP4_95-137 self-associates into a parallel, tetrameric coiled-coil, with the hydrophobic core interrupted by three polar layers occupying a and d-heptad positions. Side-chains from two consecutive polar layers, consisting of four Gln123 and two of the four Glu120 residues, coordinate a divalent cation. Two independent structures built from MAD-phased data indicated the presence of a strontium and calcium ion bound at this site, respectively. This metal-binding site appears to play an important role in stabilizing the homo-tetramer, which has implications for the engagement of NSP4 as an enterotoxin.