Positional Dependence, Cliques, and Predictive Motifs in the bHLH Protein Domain

Abstract

Quantitative analyses were carried out on a large number of proteins that contain the highly conserved basic helix-loop-helix domain. Measures derived from information theory were used to examine the extent of conservation at amino acid sites within the bHLH domain as well as the extent of mutual information among sites within the domain. Using the Boltzmann entropy measure, we described the extent of amino acid conservation throughout the bHLH domain. We used position association (pa) statistics that reflect the joint probability of occurrence of events to estimate the "mutual information content" among distinct amino acid sites. Further, we used pa statistics to estimate the extent of association in amino acid composition at each site in the domain and between amino acid composition and variables reflecting clade and group membership, loop length, and the presence of a leucine zipper. The pa values were also used to describe groups of amino acid sites called "cliques" that were highly associated with each other. Finally, a predictive motif was constructed that accurately identifies bHLH domain-containing proteins that belong to Groups A and B.

Insulin-activated Erk-mitogen-activated Protein Kinases Phosphorylate Sterol Regulatory Element-binding Protein-2 at Serine Residues 432 and 455 in Vivo

“…Structural features of the transcription factors SREBPs show that they belong to the basic helix-loop-helix leucinezipper (bHLH-LZ) super-family (17,18). Most bHLH-LZ proteins bind as either homo-or hetero-dimers to a consensus DNA sequence.…”

Two novel missense mutations in HAIRY-AND-ENHANCER-OF-SPLIT-7 in a family with spondylocostal dysostosis

“…Longo et al 18 compared the crystal structures of the E47 homodimer and the E47-NeuroD heterodimer. In these structures, the residue homologous to I58 (IleH2.4 in the universal nomenclature of Atchley et al 19 ) is spatially close to amino acids LeuH1.10, PheH1.7 and LysH2.1 of E47. Of these residues, it is unlikely that the I58V mutation will alter the interaction with LeuH1.10.…”

Soybean SAT1 ( Symbiotic Ammonium Transporter 1 ) encodes a bHLH transcription factor involved in nodule growth and NH 4 + transport

“…S6A), a phenotype that explains the ability of GmbHLHm1 (SAT1) to complement growth of yeast mutants 26972c but not 31019b on low NH 4 + concentrations. Because MEP3 does not present E-box binding domains (6) in its promoter region, the enhanced expression by GmbHLHm1 may be indirect. This could be mediated by altered cellular NH 4 + homeostasis influenced by the GmbHLHm1-enhanced expression of the NH 4 + channel ScAMF1, which our data indicate is responsible for both MA uptake and MA toxicity when GmbHLHm1 is expressed in either 26972c (3) or 31019b (Fig.…”