Mechanism of DNA Binding Enhancement by Hepatitis B Virus Protein pX

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• 作者：C. Rodgers Palmer ; Laura D. Gegnas ; and Alanna Schepartz
• 刊名：Biochemistry
• 出版年：1997
• 出版时间：December 9, 1997
• 年：1997
• 卷：36
• 期：49
• 页码：15349 - 15355
• 全文大小：208K
• 年卷期：v.36,no.49(December 9, 1997)
• ISSN：1520-4995

文摘

At least three hundred million people worldwide are infected withthe hepatitis B virus (HBV),and epidemiological studies show a clear correlation between chronicHBV infection and the developmentof hepatocellular carcinoma. HBV encodes a protein, pX, whichabducts the cellular transcriptionalmachinery in several ways including direct interactions with bZIPtranscription factors. These interactionsincrease the DNA affinities of target bZIP proteins in a DNAsequence-dependent manner. Here we usea series of bZIP peptide models to explore the mechanism by which pXinteracts with bZIP proteins.Our results suggest that pX increases bZIP·DNA stability byincreasing the stability of the bZIP dimer aswell as the affinity of the dimer for DNA. Additional experimentsprovide evidence for a mechanism inwhich pX recognizes the composite structure of the peptide·DNAcomplex, not simply the primary peptidesequence. These experiments provide a framework for understandinghow pX alters the patterns oftranscription within the nucleus. The similarities between themechanism proposed for pX and themechanism previously proposed for the human T-cell leukemia virusprotein Tax are discussed.