Proposed structure for the DNA-binding domain of the helix-loop-helix family of eukaryotic gene regulatory proteins.
A modelled tertiary structure for the dimeric HLH domain of the E47 protein is presented. Structural information was obtained from the aligned sequences of > 40 members of the HLH family. The information was used to model each monomer as an alpha-helical hairpin, with knobs-into-holes packing of side-chains as found in antiparallel coiled-coil. The dimer forms a four-helix bundle with additional knobs-into-holes packing at the dimer interface. The size and electrostatic properties of core-forming residues are all accounted for in the model. The model does not violate any known properties of protein structure. The monomers are related by two-fold rotational symmetry, in agreement with the observed DNA-binding sites which are imperfect inverted repeats. The N-terminal basic region, in which DNA binding and base specificity reside, forms the first part of helix 1. A prediction based on the model structure is that the HLH domains do not bind to DNA in its B form but require a partially unwound conformation in order to enter the major groove.
Gibson
T J
TJ
European Molecular Biology Laboratory, Heidelberg, Germany.
Thompson
J D
JD
Abagyan
R A
RA
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry; D001665:Binding Sites; D003198:Computer Simulation; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D008432:Mathematical Computing; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins; D012091:Repetitive Sequences, Nucleic Acid; D016415:Sequence Alignment; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D016601:RNA-Binding Proteins; C054243:Rop protein, ColE1 plasmid; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; D004247:DNA