HELIX- TURN- HELIX&

HELIX- LOOP- HELIX

BIOTECHNOLOGY

- BY- NAREN YADAV

DNA – Binding Domain

A DNA-binding domain (DBD) is an independently folded protein domain that contains at least one motif that recognizes double- or single-stranded DNA. A DBD can recognize a specific DNA sequence (a recognition sequence) or have a general affinity to DNA.

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Types of DNA-Binding Motifs

• 1. Steroid Receptor

• 2. Zinc Fingers

• 3. Leucine Zipper

• 4. Homeodomain

• 5.HELIX-TURN-HELIX

• 6.HELIX-LOOP-HELIX

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Helix-turn-helix

• In proteins, the helix-turn-helix (HTH) is a major structural motif capable of binding DNA.

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DISCOVERY

• The discovery of the helix-turn-helix motif was based on similarities between several genes encoding transcription regulatory proteins from bacteriophagelambda and Escherichia coli: Cro, CAP, and λ repressor, which were found to share a common 20-25 amino acid sequence that facilitates DNA recognition.

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EXAMPLE

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The λ repressor of bacteriophagelambda employs a helix-turn-helix (left; green) to bindDNA (right; blue and red).

STRUCTURE

• The structure consist of two α helices joined by a short strand of amino acid.

• The recognition and binding to DNA by helix-turn-helix proteins is done by the two α helices, one occupying the N-terminal end of the motif, the other at the C-terminus.

• In most cases, such as in the Crorepressor, the second helix contributes most to DNA recognition, and hence it is often called the "recognition helix".

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Helix-turn-helix

C-terminal binds to major groove, N-terminal

helps to position the complex

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FUNCTION

The helix-turn-helix (HTH) is a major structural motif capable of binding DNA. It is found in many proteins that regulate gene expression.

It binds to the major groove of DNA through a series of hydrogen bonds and various Van der Waals interactions with exposed bases. The other α helix stabilizes the interaction between protein and DNA, but does not play a particularly strong role in its recognition.

The recognition helix and its preceding helix always have the same relative orientation.

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CLASSIFICATION OF HELIX

TURN HELIX

Di-helical

Tri-helical

Tetra-helical

Winged helix-turn-helix

Other modified helix-turn-helix motifs

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Helix-turn-helix

review

LOCATION•Bacterial

regulatory proteins,

•Related motifs in eukaryotic proteins.

CHARACTERIST-ICS

•Two alpha helices

BINDING SITE IN DNA

•Major groove

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Helix-loop-helix

- The helix-loop-helix binding motif consists of two alpha helices separated by a loop of amino acids.

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STRUCTURE

-Two polypeptide chains with the motif join to form a functional DNA-binding protein.

- A highly basic set of amino acids in one of the helices binds to the DNA.

- Transcription factor including this domain are in dimeric form.

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CONTINUE…

• 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.

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FUNCTION

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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 constitutively expressed.

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Helix-loop-helix

review

LOCATION

•Eukaryotic protein

CHARACTERIST-ICS

•Two alpha helices separated by a loop of amino acids.

BINDING SITE IN DNA

•Major groove

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EXAMPLES

• AhR,BMAL-1-CLOCK,C-Myc,

• N-Myc,MyoD,Myf5,Scleraxis,

• Neurogenis, etc…

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•THANK YOU

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