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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