人类乙型肝炎样病毒核心蛋白中第7位疏水性氨基酸重复肚段区域的突变可以抑制病毒核衣壳的组装

人类乙型肝炎病毒的核衣壳由核心蛋白的二聚体所组成．但是，核心蛋白亚单位与亚单位之间相互作用的机制至今尚不清楚．研究发现，在人类乙型肝炎样病毒──土拨鼠肝炎病毒（WHV）核心蛋白的氨基端，存在着4个保守的疏水氨基酸残基（氨基酸位置101～102）．它们分别是亮氨酸101，亮氨酸108，缬氨酸115和苯丙氨酸122．这4个疏水氨基酸残基以每隔6个氨基酸残基而重复出现1次．它们被称为“第7位疏水性氨基酸重复肽段（hhr）”．由于蛋白质中的疏水键往往在蛋白质的相互作用中起重要作用，因此就在培养细胞系统中研究WHV核心蛋白的hhr区域在…

Mutations in a Hydrophobic Heptad Repeat Region of the Core Protein inhibited Capsid Assembly of The Human Hepatitis B-Like Virus

The nucleocapsid of hepadnaviruses consisits of dimers of the core proteins. However, the mechanism of the core-core subunit interaction is not well understood. The Nterminus of the core protein of woodchuck hepatitis virus(WHV) was found containing four conserved hydrophobic amino acid residues (from residue 101 to 122 ). These residues, referred to the hydrophobic heptad repeat(hhr), distributed as heptad repeats in the primary sequence. Since hydrophobic bounds often play an important role in interaction of proteins, roles of the hhr region in capsid assembly of WHV were investigated using a cell culture system. The codons for these four hydrophobic amino acid residues and other related residues in this region were substituted with codons specifying alanine or proline. Phenotype of each of these mutants was examined at various stages of viral replication in Hub7 cells. It was found that single substitution of the four hydrophobic residues had no detectable effect, but substitution of the same residues in various paired combinations resulted in a complete inhibition of capsid assembly. The capsid assembly was inhibited when amino acid insertion occerred at the first and last two hydrophobic residues or a single amino acid deletion occurred at the first pair of hydrophobic residues. However, random amino acid substitutions in this region did not affect assembly. The results indicated that the hhr region of the core protein was necessory for capsid assembly of woodchuck hepatitis virus.