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Cell. 1993 Feb 12;72(3):467-76.

High affinity DNA-binding Myc analogs: recognition by an alpha helix.

Author information

1
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.

Abstract

Myc and other basic-helix-loop-helix-leucine zipper (b-HLH-ZIP) proteins bind the sequence CACGTG. Exhaustive mutagenesis in the basic domain identified four amino acids critical for DNA binding with spacing suggestive of an alpha-helical face. Surprisingly, two highly conserved amino acids were nonessential for DNA binding. Circular dichroism demonstrated a DNA-induced alpha-helical transition. A series of analogs were constructed with multiple simultaneous alanine substitutions at nonessential positions and a critical lysine for arginine substitution. In this way 35-fold higher specific affinity for CACGTG was obtained as compared with the basic domain of c-Myc. These b-HLH-ZIP proteins appear to bind the same palindromic sequence and may compete for common sites in vivo. Additionally, a C-terminal basic region clamp motif was identified that was also identifiable in crystal structures from several different families of DNA-binding factors.

PMID:
8431949
DOI:
10.1016/0092-8674(93)90122-7
[Indexed for MEDLINE]

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