Mechanism of DNA-binding enhancement by the human T-cell leukaemia virus transactivator Tax.
Tax protein activates transcription of the human T-cell leukaemia virus type I (HTLV-I) genome through three imperfect cyclic AMP-responsive element (CRE) target sites located within the viral promoter. Previous work has shown that Tax interacts with the bZIP element of proteins that bind the CRE target site to promote peptide dimerization, suggesting an association between Tax and bZIP coiled coil. Here we show that the site of interaction with Tax is not the coiled coil, but the basic segment. This interaction increases the stability of the GCN4 bZIP dimer by 1.7 kcal mol-1 and the DNA affinity of the dimer by 1.9 kcal mol-1. The differential effect of Tax on several bZip-DNA complexes that differ in peptide sequence or DNA conformation suggests a model for Tax action based on stabilization of a distinct DNA-bound protein structure. This model may explain how Tax interacts with transcription factors of considerable sequence diversity to alter patterns of gene expression.
Baranger
A M
AM
Department of Chemistry, Yale University, New Haven, Connecticut 06520, USA.
Palmer
C R
CR
Hamm
M K
MK
Giebler
H A
HA
Brauweiler
A
A
Nyborg
J K
JK
Schepartz
A
A
D000595:Amino Acid Sequence; D001483:Base Sequence; D000242:Cyclic AMP / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D015342:DNA Probes; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000378:metabolism; D016356:Gene Products, tax / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D016350:Leucine Zippers; D008954:Models, Biological; D008969:Molecular Sequence Data; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins
D015342:DNA Probes; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D016356:Gene Products, tax; D029701:Saccharomyces cerevisiae Proteins; D004247:DNA; D000242:Cyclic AMP; D011494:Protein Kinases