Basic-helix-loop-helix

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Image:Basic helix loop helix.png
bHLH structural motif of the AhR protein: two α helices (blue) connected by a loop (red)

A basic-helix-loop-helix (bHLH) is a protein structural motif that characterizes a family of transcription factors.

Structure

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 [1]. 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 [1]. 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

Examples of transcription factors containing a bHLH include:

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.

Regulation

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, whereas the other subunit is constituitively expressed. Many of the known regulatory proteins, such as the Drosophila extramacrochaetae protein, have the helix-loop-helix structure but lack the basic region, making them unable to bind to DNA on their own. They are, however, able to form heterodimers with proteins that have the bHLH structure, and inactivate their abilities as transcription factors [1].

History

  • 1989: Murre et al. could show that dimers of various bHLH proteins bind to a short DNA motif (later called E-Box)[1]. This E-box consists of the DNA sequence CANNTG, where N can be any nucleotide [1].

References


External links

de:Helix-loop-helix-Transkriptionsfaktoren

Acknowledgement and Attribution Regarding Sources of Content

Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .

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