9316719 Santiago The cAMP responsive element binding protein (CREB) is a DNA binding protein required for the transcription of the somatostatin gene. This protein's usual narrow DNA binding selectivity is broadened upon heterodimer formation with the pX protein (from hepatitis B virus). Two dimensional NMR spectroscopy will be utilized to characterize this change in DNA binding specificity. Specific aims include: (1) characterize the CREB:DNA interaction, (2) Determine the solution structure of chimeric CREB peptides that exhibit DNA binding similar to the native CREB, and (3) attempt to modify DNA recognition by CREB homodimers. %%% DNA-protein interactions are of fundamental importance to the control of cell physiology. The leucine zipper is a structural element found in many DNA-binding proteins. Structural studies of many leucine zipper structures have established the ground rules for specific recognition of DNA by zipper dimers. The CREB protein (cyclic AMP responsive element binding protein): DNA interaction is itself modulated by interactions with a protein from hepatitis B virus. Of major importance is development of an understanding of the modulation of the binding specificity of a zipper:DNA interaction. This study could point the way to a broader understanding of the control of gene expression. ***
