Stephen J. Stahl

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Despite the development of vaccines, the hepatitis B virus remains a major cause of human liver disease. The virion consists of a lipoprotein envelope surrounding an icosahedral capsid composed of dimers of a 183-residue protein, 'core antigen' (HBcAg). Knowledge of its structure is important for the design of antiviral drugs, but it has yet to be(More)
Using heteronuclear NMR spectroscopy, we demonstrate that a 13-residue peptide (MS-QIKRLLSEKKT) from the cytoplasmic tail of CD4 binds to Nef protein. This part of CD4 is critical for downregulation of CD4 by HIV-1 Nef [Aiken et al. (1994) Cell 76, 853-864]. We show that a control peptide without the central dileucine does not bind to Nef. The dependence of(More)
The capsids of most spherical viruses are icosahedral, an arrangement of multiples of 60 subunits. Though it is a salient point in the life cycle of any virus, the physical chemistry of virus capsid assembly is poorly understood. We have developed general models of capsid assembly that describe the process in terms of a cascade of low order association(More)
The three-dimensional solution structure of a complex between the DNA binding domain of the chicken erythroid transcription factor GATA-1 and its cognate DNA site has been determined with multidimensional heteronuclear magnetic resonance spectroscopy. The DNA binding domain consists of a core which contains a zinc coordinated by four cysteines and a(More)
The solution structure of HIV-1 Nef has been solved by multidimensional heteronuclear NMR spectroscopy. The construct employed to circumvent problems associated with aggregation was a double-deletion mutant (delta2-39, delta159-173) in which conformationally disordered regions of the protein at the N terminus and in a long solvent-exposed flexible loop were(More)
Nuclear export of unspliced and singly spliced viral mRNA is a critical step in the HIV life cycle. The structural basis by which the virus selects its own mRNA among more abundant host cellular RNAs for export has been a mystery for more than 25 years. Here, we describe an unusual topological structure that the virus uses to recognize its own mRNA. The(More)
HIV-1 Rev is a small regulatory protein that mediates the nuclear export of viral mRNAs, an essential step in the HIV replication cycle. In this process Rev oligomerizes in association with a highly structured RNA motif, the Rev response element. Crystallographic studies of Rev have been hampered by the protein's tendency to aggregate, but Rev has now been(More)
The high-level expression of HIV-1 Rev in Escherichia coli is described. Protein in crude bacterial extracts was dissociated from bound nucleic acid with urea. A simple purification and renaturation protocol, monitored by circular dichroism, is described which results in high yields of pure protein. The purified protein binds with high affinity to the(More)
Hepatocyte growth factor/scatter factor (HGF/SF) is a heparin-binding polypeptide that stimulates cell proliferation, motility, and morphogenesis by activation of its receptor, the c-Met tyrosine kinase. HGF/SF consists of a series of structural units, including an amino-terminal segment with a hairpin loop, four kringle domains, and a serine protease-like(More)
The production and biochemical and physiocochemical analysis are described of recombinant-produced hepatitis B virus core antigen (HBcAg capsid) and the corresponding particle produced by a deletion mutant missing the C-terminal 39 residues (HBeAg). Conditions for producing HBeAg from HBcAg capsids by in vitro proteolysis are also described. The morphology(More)