THE SOLUTION STRUCTURE OF THE LEUCINE-ZIPPER MOTIF OF THE JUN ONCOPROTEIN HOMODIMER

Proton NMR studies have been performed on a 9.8-kDa synthetic fragment comprising the homodimeric leucine zipper domain of the human oncopro tein Jun to ascertain its conformation in aqueous solution. Analysis o f two-dimensional scalar and dipolar-coupling experiments enabled almo st all proton resonances to be sequence-specifically assigned and furt her revealed that the Jun leucine zipper forms a completely symmetric dimer in solution, consistent with the formation of a coiled-coil arra ngement of parallel alpha-helical strands. The rates of exchange of in dividual amide protons with solvent, as well as hydrogen-bond lengths predicted from amide proton chemical shifts, are shown to correlate wi th residue position in the coiled-coil. A subset of 209 unambiguous di stance constraints was compiled using rules recently formulated for in terpreting the NOESY spectra of symmetric coiled-coils, and these were used in combination with experimentally determined hydrogen bond and dihedral angle constraints to compute a solution structure for the Jun leucine zipper domain.