Molecular Determinants for Subcellular Localization of Hepatitis C Virus Core Protein

作者: Ryosuke Suzuki , Shinichiro Sakamoto , Takeya Tsutsumi , Akiko Rikimaru , Keiko Tanaka

DOI: 10.1128/JVI.79.2.1271-1281.2005

关键词: Nuclear localization sequenceCell nucleusSubcellular localizationBiologyBiochemistryEndoplasmic reticulumNuclear proteinVesicle-associated membrane protein 8Fusion proteinCytoplasm

摘要: Hepatitis C virus (HCV) core protein is a putative nucleocapsid with number of regulatory functions. In tissue culture cells, HCV mainly located at the endoplasmic reticulum as well mitochondria and lipid droplets within cytoplasm. However, it also detected in nucleus some cells. To elucidate mechanisms by which cellular trafficking controlled, we performed subcellular fractionation experiments used confocal microscopy to examine distribution heterologously expressed fusion proteins involving various deletions point mutations combined green fluorescent proteins. We demonstrated that region spanning amino acids 112 152 can mediate association not only ER but mitochondrial outer membrane. This contains an 18-amino-acid motif predicted form amphipathic α-helix structure. With regard nuclear targeting protein, identified novel bipartite localization signal, requires two out three basic-residue clusters for efficient translocation, possibly occupying binding sites on importin-α. Differences achieved maintained multiple functions mentioned above, may part regulate diverse range biological roles protein.

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