Non-leucine residues in the leucine repeats of Fos and Jun contribute to the stability and determine the specificity of dimerization.
Various transcription factors, including C/EBP, GCN4 and members of the Fos, Jun and Myc families have been shown to form highly specific complexes via alpha-helical structures referred to as leucine zippers. Experimental evidence has suggested that dimerization involves the formation of hydrophobic bonds between leucine residues in laterally aligned coiled coil structures. However, the specificity of interaction between leucine zipper proteins is not understood. In this study, we show that amino acids, which are located in positions a, e, and g are instrumental in the formation of Fos/Jun heterodimers, presumably by establishing intermolecular electrostatic and hydrophobic interactions. These residues are highly conserved in proteins of the Fos or Jun families but completely different between Fos and Jun, suggesting that these residues determine the specificity of interaction. This conclusion is supported by the observation that the substitution of amino acids in position a or g in Fos with the corresponding Jun amino acids facilitates the association of two Fos leucine repeats. In addition, we show that a conserved histidine residue, located 7 amino acids (i.e., two alpha-helical turns) C-terminally to the 5th leucine in Fos and Jun, is also important for complex formation.
Schuermann
M
M
Institut für Molekularbiologie und Tumorforschung (IMT), Phillipps-Universität Marburg, FRG.
Hunter
J B
JB
Hennig
G
G
Müller
R
R
D000595:Amino Acid Sequence; D004591:Electrophoresis, Polyacrylamide Gel; D016350:Leucine Zippers / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D016759:Oncogene Protein p65(gag-jun); D016761:Oncogene Proteins v-fos; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D013379:Substrate Specificity; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D016759:Oncogene Protein p65(gag-jun); D016761:Oncogene Proteins v-fos; D009856:Oncogene Proteins, Viral; D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors