The oncoproteins Fos and Jun form heterodimers through a leucine zipper interaction. The heterodimer contains one Fos helix and one Jun helix. Each protein also contains a region that binds DNA. (The Fos-Jun heterodimer functions as a transcription factor.) It can be viewed at https://www.rcsb.org/3d-view/1FOS/1.

a. Is the leucine zipper at the C-terminus or at the N-terminus of Fos? How about for Jun? Are the helices parallel or antiparallel?

b. Remember that in a leucine zipper, there is a heptad (seven-residue) repeat, with conserved leucine residues occupying the d positions within the repeats. Label each of the residues in each sequence as a, b, c, d, e, f, and g positions.

Fos: LQAETDQLEDEKSALQTEIANLLKEKEKLEFILAAH

Jun: LEEKVKTLKAQNSELASTANMLREQVAQLKQKVMNH

c. Examine the end of the structure thats farthest from the DNA. You should be able to match part of the protein structure to the leucine zipper sequences below, although some of the amino acids may be missing or only partially visible. On the sequences below: Box (or designate in some other obvious way) the ten residues of each monomer that are farthest from the DNA. Then cross out those residues within the box where the side chain is not fully visible in the structure.

Fos: LQAETDQLEDEKSALQTEIANLLKEKEKLEFILAAH

Jun: LEEKVKTLKAQNSELASTANMLREQVAQLKQKVMNH

d. Examine the dimer interface at the end of the structure farthest from the DNA. On the sequences below, indicate with asterisks those residues (within the ten residues farthest from the DNA) that contribute to the hydrophobic core of the heterodimer. Describe an instance (among your asterisked residues) where an amphipathic residue contributes to the hydrophobic core. Which part of this residue packs in the core?

Fos: LQAETDQLEDEKSALQTEIANLLKEKEKLEFILAAH

Jun: LEEKVKTLKAQNSELASTANMLREQVAQLKQKVMNH