Basic helix-loop-helix

A basic helix-loop-helix (bHLH) is a protein structural motif that characterizes one of the largest families of dimerizing transcription factors. A basic helix-loop-helix (bHLH) is a protein structural motif that characterizes one of the largest families of dimerizing transcription factors. bHLH transcription factors are often important in development or cell activity. BMAL1-Clock is a core transcription complex in the molecular circadian clock. Other genes, like c-Myc and HIF-1, have been linked to cancer due to their effects on cell growth and metabolism. It should not be confused with the helix-turn-helix domain. The motif is characterized by two α-helices connected by a loop. In general, transcription factors including this domain are dimeric, each with one helix containing basic amino acid residues that facilitate DNA binding. In general, one helix is smaller, and, due to the flexibility of the loop, allows dimerization by folding and packing against another helix. The larger helix typically contains the DNA-binding regions. bHLH proteins typically bind to a consensus sequence called an E-box, CANNTG. The canonical E-box is CACGTG (palindromic), however some bHLH transcription factors, notably those of the bHLH-PAS family, bind to related non-palindromic sequences, which are similar to the E-box. bHLH TFs may homodimerize or heterodimerize with other bHLH TFs and form a large variety of dimers, each one with specific functions. A phylogenetic analysis suggested that bHLH proteins fall into 6 major groups, indicated by letters A through F. Examples of transcription factors containing a bHLH include: These proteins contain two additional PAS domains after the bHLH domain.