Identification of functionally important amino acid residues in the mitochondria targeting sequence of hepatitis B virus X protein.
Chronic hepatitis B virus (HBV) infection has been strongly associated with hepatocellular carcinoma (HCC) and the X protein (HBx) is thought to mediate the cellular changes associated with carcinogenesis. Recently, isolation of the hepatitis B virus integrants from HCC tissue by others have established the fact that the X gene is often truncated at its C-terminus. Expression of the GFP fusion proteins of HBx and its truncation mutants with a GFP tag in human liver cell-lines in this study revealed that the C-terminus of HBx is indispensable for its specific localization in the mitochondria. A crucial region of seven amino acids at the C-terminus has been mapped out in which the cysteine residue at position 115 serves as the most important residue for the subcellular localization. When cysteine 115 of HBx is mutated to alanine the mitochondria targeting property of HBx is abrogated.
Li
Sai Kam
SK
Croucher Laboratory for Human Genomics, Chinese University of Hong Kong, Shatin, N.T., Hong Kong, S.A.R., China.
Ho
Sai Fan
SF
Tsui
Kwok Wing
KW
Fung
Kwok Pui
KP
Waye
M Y Mary
MY
D000596:Amino Acids / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000821:virology; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D049452:Green Fluorescent Proteins / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation; D021381:Protein Transport; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
D000596:Amino Acids; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D049452:Green Fluorescent Proteins