c-Myc and Max are members of a subfamily of the helix-loop-helix transcription-regulating proteins. Their function is mediated by switches in the dimerization partners; c-Myc does not homodimerize in vivo but competes with Mad, another member of the subfamily, to form heterodimers with Max, leading to either activation or repression of transcription. Max is also able to form homodimers. In an attempt to identify which regions of the proteins carry the information to determine specific recognition of the dimerization partner, we have investigated the dimerization properties of synthetic peptides corresponding to the leucine zipper sequence of Max and c-Myc using circular dichroism and nuclear magnetic resonance techniques. We show that the heterodimer is obtained readily by simply mixing the peptides and that at neutral pH it is more stable than the homodimer of the Max leucine zipper. We have shown in a previous paper [Muhle-Goll, C. et al. (1994) Biochemistry 33, 11296-11306] that the leucine zipper of c-Myc does not form stable homodimers under these conditions. Thus, the leucine zipper regions of these two proteins by themselves display the same behavior as the entire proteins. However, even the heterodimer is less stable than dimers of leucine zippers of the basic leucine zipper family such as GCN4 and Fos-Jun. The specificity of the interaction between different monomers can be explained by polar interactions. We investigate the structural role of the polar and charged residues in the hydrophobic interface by molecular-modeling studies.

The leucine zippers of the HLH-LZ proteins Max and c-Myc preferentially form heterodimers

Pastore A
1995

Abstract

c-Myc and Max are members of a subfamily of the helix-loop-helix transcription-regulating proteins. Their function is mediated by switches in the dimerization partners; c-Myc does not homodimerize in vivo but competes with Mad, another member of the subfamily, to form heterodimers with Max, leading to either activation or repression of transcription. Max is also able to form homodimers. In an attempt to identify which regions of the proteins carry the information to determine specific recognition of the dimerization partner, we have investigated the dimerization properties of synthetic peptides corresponding to the leucine zipper sequence of Max and c-Myc using circular dichroism and nuclear magnetic resonance techniques. We show that the heterodimer is obtained readily by simply mixing the peptides and that at neutral pH it is more stable than the homodimer of the Max leucine zipper. We have shown in a previous paper [Muhle-Goll, C. et al. (1994) Biochemistry 33, 11296-11306] that the leucine zipper of c-Myc does not form stable homodimers under these conditions. Thus, the leucine zipper regions of these two proteins by themselves display the same behavior as the entire proteins. However, even the heterodimer is less stable than dimers of leucine zippers of the basic leucine zipper family such as GCN4 and Fos-Jun. The specificity of the interaction between different monomers can be explained by polar interactions. We investigate the structural role of the polar and charged residues in the hydrophobic interface by molecular-modeling studies.
1995
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11384/77022
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 47
  • ???jsp.display-item.citation.isi??? 45
social impact