Palmer C R, Gegnas L D, Schepartz A
Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107, USA.
Biochemistry. 1997 Dec 9;36(49):15349-55. doi: 10.1021/bi972076m.
At least three hundred million people worldwide are infected with the hepatitis B virus (HBV), and epidemiological studies show a clear correlation between chronic HBV infection and the development of hepatocellular carcinoma. HBV encodes a protein, pX, which abducts the cellular transcriptional machinery in several ways including direct interactions with bZIP transcription factors. These interactions increase the DNA affinities of target bZIP proteins in a DNA sequence-dependent manner. Here we use a series of bZIP peptide models to explore the mechanism by which pX interacts with bZIP proteins. Our results suggest that pX increases bZIP.DNA stability by increasing the stability of the bZIP dimer as well as the affinity of the dimer for DNA. Additional experiments provide evidence for a mechanism in which pX recognizes the composite structure of the peptide.DNA complex, not simply the primary peptide sequence. These experiments provide a framework for understanding how pX alters the patterns of transcription within the nucleus. The similarities between the mechanism proposed for pX and the mechanism previously proposed for the human T-cell leukemia virus protein Tax are discussed.
全球至少有3亿人感染了乙肝病毒（HBV），流行病学研究表明，慢性HBV感染与肝细胞癌的发生之间存在明显的相关性。HBV编码一种蛋白质pX，它通过多种方式劫持细胞转录机制，包括与bZIP转录因子直接相互作用。这些相互作用以DNA序列依赖的方式增加了靶bZIP蛋白的DNA亲和力。在这里，我们使用一系列bZIP肽模型来探索pX与bZIP蛋白相互作用的机制。我们的结果表明，pX通过增加bZIP二聚体的稳定性以及二聚体对DNA的亲和力来提高bZIP.DNA的稳定性。额外的实验为一种机制提供了证据，即pX识别肽.DNA复合物的复合结构，而不仅仅是初级肽序列。这些实验为理解pX如何改变细胞核内的转录模式提供了一个框架。文中还讨论了pX所提出的机制与先前为人T细胞白血病病毒蛋白Tax所提出的机制之间的相似性。
