-
Views
-
Cite
Cite
Toby J. Gibson, Julie D. Thompson, Ruben A. Abagyan, Proposed structure for the DNA-binding domain of the Helix—Loop—Helix family of eukaryotic gene regulatory proteins, Protein Engineering, Volume 6, Issue 1, January 1993, Pages 41–50, https://doi.org/10.1093/protein/6.1.41
Close - Share Icon Share
Abstract
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 α-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.
