FC0045
Neurogenin 1 (NGN1)  -  DNA

Biological function
Neurogenin 1 (NGN1) is a 237-residue transcription factor which is involved in neuronal differentiation.

Domain organization/sequence features
It contains a bHLH (basic helix-loop-helix) domain, which are generally disordered in the absence of DNA. The typical bHLH domain is approximately 60 residues long, comprising a DNA-binding basic region followed by two α-helices separated by a variable loop region (and, hence, the name HLH). The consensus DNA sequence targeted by several bHLH proteins is the hexameric 5^’ -CANNTG-3^’ element, referred to as ‘E-box’.

Structural evidence
NGN1 forms homodimers (as suggested by fluorescence titrations) upon interacting with the E-boxes. The protein does not fold completely upon binding to DNA as corroborated by CD, FTIR, DOSY-NMR, and 1D-NMR studies, although some increase in structure has been observed.

Biochemical evidence
The affinities of bHLHN for both DNA boxes were smaller than those of other bHLH domains. The affinity for the E1-box was 8.1 μM), and that for the E3-box was 0.9 μM, in contrast to 1-30 nM for other bHLH domains.

Structure/Mechanism
The bound state should be chosen through selection of a conformer, which was sampled in the residual secondary structure adopted by the isolated bHLHN in solution: that is, the helical region at the C-terminus of the domain.

Mechanism category
conformational selection

Significance
Degree of fuzziness can control specificity of the protein.

Submitted by
José Luis Neira Faleiro    jlneira@umh.es