DNA binding sites are a part of DNA molecule where other molecules can bind. DNA binding proteins recognize and bind this portion of the nucleotide sequence. They are short DNA sequences of about 4 to 30 bp surrounded by DNA BINDING PROTEINS or Protein complexes. The binding is the result of extensive complementarity between the DNA binding motifs and the protein surface.

The DNA binding proteins have a specific folding pattern which is made of repeated nucleotide sequences called as DNA binding motifs. These motifs permit the binding of DNA binding proteins such as transcription factors to the target sequence. It is composed of recognition region and stabilization region.

Recognition of the DNA sequence can be either due to Specific binding or non specific binding. Specific binding is between protein side chains and DNA sugar/phosphate backbone whereas non specific binding is between protein side chains and nucleotide bases. Binding occurs at the minor or major grooves of the DNA. However, base specific binding often occurs at the major groove of the DNA.

TYPES OF MOTIFS:

There are mainly four types of DNA Binding Motifs:
• Helix Turn Helix Motif
• Helix Loop Helix Motif
• Leucine Zipper Motif
• Zinc Finger Motif

HELIX TURN HELIX MOTIF:

It is the first discovered and most extensively studied DNA binding motif. Helix turn helix motif is generally found in prokaryotic DNA and is mainly found in repressor protein. This motif is about 20 amino acids long and regulates gene expression at the transcription level. The motif was first identified in bacteria. These helices are common in proteins involved in regulating the development processes.

Examples include Lac repressor and CAP in E.Coli, Cro and Tryptophan in Phages, and homeobox proteins. The basic motif comprises two alpha helices with a beta turn in between. The beta turn comprises four aminoacids of which the second is usually glycine. The second alpha helix is positioned in such a way so as to fit inside the major groove of the DNA double helix. This C-terminal alpha helix is called the recognition helix since it is involved in sequence specific recognition of DNA. N-terminal helix helps to position the complex.

The 3-D structure of Cro has revealed the monomer units containing 3 anti parallel beta sheets and 3 alpha helices. The alpha helices are shown to form the recognition surface whereas others are found to stabilize the structure. The DNA recognition domain of each Cro monomer interacts with 5 bp and the dimer binding site span 3.4nm, allowing fit into successive half turns of the major groove on the same surface.

The homeodomains are an extended helix turn helix motif. They bind to "homeoboxes", 180 bp DNA sequences which code for 60 aminoacids. The motif has four alpha helices with a beta turn which separates the second and third alpha helices. The third one acts as the recognition sequence and the first alpha helix with the N-terminus form an arm which inserts into the minor groove of the DNA helix.

HELIX LOOP HELIX MOTIF

This motif is involved in protein dimerization. They are super secondary structures characterized by two alpha helices comprising 20 amino acids each separated by a non helical loop segment of variable length. One loop is smaller than the other. The smaller loop allows dimerization by folding and packing against the other helix whereas larger helix contains the DNA binding regions.

They are commonly found in many DNA-Binding proteins and in Calcium binding proteins. Occasionally they allow the formation of heterodimers. Examples include transcription factors Myc/Max and USF which contain both HLH and LZ motifs. The HLH motif gets inactivated on truncation of its tail i.e. the DNA binding domain.

Winged Helix - It consists of 110 amino acids and has 4 helices and a two strand beta sheets.
Winged Helix Turn Helix: It has 85 to 90 amino acids and 3 helical bundle and 4 beta strand sheets.
HMG Box: It has 3 alpha helices separated by loops and is generally found in high mobility proteins which are involved in DNA dependent processes like replication and transcription.

There are other DNA binding motifs such as Zinc fingers and Leucine Zipper motifs which are detailed in the next part of this article.

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