HIGH-RESOLUTION NMR SOLUTION STRUCTURE OF THE LEUCINE-ZIPPER DOMAIN OF THE C-JUN HOMODIMER

The solution structure of the c-Jun leucine zipper domain has been det ermined to high resolution using a new calculation protocol designed t o handle highly ambiguous sets of interproton distance restraints, The domain comprises a coiled coil of parallel alpha-helices in which mos t of the hydrophobic residues are buried at the highly symmetrical dim er interface; this Interface extends over 10 helical turns and is the most elongated protein domain solved to date using MMR methods, The ba ckbone fold is very similar to that seen in crystal structures of the GCN4 and Jun-Fos leucine zippers; however, in contrast with these crys tal structures, the Jun leucine zipper dimer appears to be devoid of f avorable intermolecular electrostatic interactions, A polar asparagine residue, located at the dimer interface, forms the sole point of asym metry in the structure; furthermore, the side chain of this residue is disordered due to motional averaging, This residue, which is highly c onserved in the leucine zipper family of transcription factors, provid es a destabilizing influence that is likely to facilitate the rapid ex change of zipper strands in vivo.