Basic-helix-loop-helix

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A basic-helix-loop-helix (bHLH) is a protein structural motif that characterizes a family of transcription factors. The motif is characterized by two α helices connected by a loop. Transcription factors including this domain are typically dimeric, each with one helix containing basic amino acid residues that facilitate DNA binding (Lodish et. al., 2004). One helix is typically 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 bind to different sequences, which are often similar to the E-box. Examples of transcription factors containing a bHLH include:

• AhR
• BMAL1-Clock
• c-Myc
• MyoD
• HIF
• NPAS1, MOP5
• Scl, also known as Tal1
• proneural bHLH genes like p-CaMKII, and pSer(336)NeuroD.

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. Since many bHLH transcription factors are heterodimeric, their activity is often highly regulated by the dimerization of the subunits. One subunit's expression or availability is often controlled while the other subunit is constituitively expressed.

[edit] History

• 1989 Murre et al. (PMID 2503252) could show that dimers of various bHLH proteins bind to a short DNA motif (later called E-Box).

[edit] References

Harvey Lodish, Arnold Berk, Paul Matsudaira, Chris A. Kaiser, Monty Krieger, Matthew P. Scott, Lawrence Zipursky, James Darnell: "Molecular Cell Biology", 5th edition, 2004, W.H. Freeman (ISBN 0716767783)