A protein motif is a short-conserved sequence associated with distinct functions of DNA. It is mainly associated with a special structural site with a unique chemical or biological function. These motifs contain small regions of three-dimensional structures of amino acids with different protein molecules. Usually, individual motifs contain only a few elements. Helix-loop-helix and helix-turn-helix contain three elements. Their protein structural motifs include loops with varying lengths and unspecified structures.
1. Overview and Key Difference
2. What is Helix-Loop-Helix
3. What is Helix-Turn-Helix
4. Similarities – Helix-Loop-Helix and Helix-Turn-Helix
5. Helix-Loop-Helix vs Helix-Turn-Helix in Tabular Form
6. Summary – Helix-Loop-Helix vs Helix-Turn-Helix
What is Helix-Loop-Helix?
A helix-loop-helix (HLH) is a protein structural motif that defines one of the largest families of dimerizing transcription factors. These transcription factors contain residues of amino acids to facilitate the DNA binding mechanism, and they are dimeric. The protein structural motif contains two α-helices, and they are connected by a loop. One helix appears smaller from the two helices, and the flexibility of the loop allows dimerization by packing and folding against another helix. The helix that appears larger usually contains DNA-binding regions. HLH proteins bind to a consensus sequence that is known as E-box. A consensus sequence is a calculated order containing nucleotide or amino acid residues. E-box is an element responding to DNA in some eukaryotes that acts as a protein-binding site and regulates gene expression.
The HLH transcription factors are essential for development and cell activity. HLH proteins mainly belong to six groups, which are indicated from letters A to F. The transcription factors included in each group are:
Group A: MyoD, Myf5, Beta2/NeuroD1, Scl, p-CaMK, NeuroD, and Neurogenins,
group B: MAX, C-Myc, N-Myc, and TCF4
Group C: AhR, BMAL-1-CLOCK, HIF, NPAS1, NPAS3, and MOP5
Group D; EMC
Group E: HEY1 and HEY2
Group F: EBF1
Since most transcription factors of HLH are heterodimeric, dimerization often regulates them.
What is Helix-Turn-Helix?
Helix-turn-helix (HTH) is a protein structural motif that is capable of binding DNA. Each monomer is organized with two α-helices and is joined by a short amino acid strand. This binds to a groove in the DNA helix. HTH motifs usually regulate gene expression. The HTH recognition and binding to DNA are carried out by two α-helices. One helix occupies the N-terminal end while the other is at C-terminus. In most scenarios, the helix carries out the recognition of DNA. Therefore, it is known as the recognition helix. The binding to the groove in DNA takes place through a series of Van der Waals interactions and hydrogen bonds with bases exposed. The other α-helix stabilizes the protein and DNA interaction and does not play a major role in recognition. However, the recognition helix and the remaining helix have a similar orientation.
The HTH is classified according to the structure and spatial arrangements of the helices. The main types are di-helical, tri-helical, tetra-helical, and winged HTH. Di-helical type is the simplest type with two helices and an independent folding protein domain. Tri-helical type is found in transcriptional activator Myb. Tetra-helical type has an extra C-terminal helix. Finally, the winged HTH is formed by 3- helical bundle and 3- or 4- strand beta sheet.
What are the Similarities Between Helix-Loop-Helix and Helix-Turn-Helix?
- Helix-loop-helix and helix-turn-helix are protein structural motifs.
- Both contain a common denominator in basal and specific transcription factors.
- They are present in eukaryotes.
What is the Difference Between Helix-Loop-Helix and Helix-Turn-Helix?
Helix-loop-helix mediates protein dimerization, whereas helix-turn-helix regulates gene expression through DNA binding. Thus, this is the key difference between helix-loop-helix and helix-turn-helix. Besides, HLH contains certain proto-oncogenes and genes involved in differentiation encoding transcription factors while HTH contains many homeotic genes which code for transcription factors. Moreover, helix-loop-helix mainly consists of alpha-helices joined by a loop, while helix-turn-helix mainly consists of loops joined by a short amino acid stand forming a groove.
The below infographic presents the differences between helix-loop-helix and helix-turn-helix in tabular form for side by side comparison.
Summary – Helix-Loop-Helix vs Helix-Turn-Helix
A protein motif is a short-conserved sequence associated with distinct functions of DNA. Helix-loop-helix and helix-turn-helix are two types of protein structural motifs. The key difference between helix-loop-helix and helix-turn-helix is that helix-loop-helix mediates protein dimerization, whereas helix-turn-helix regulates gene expression through DNA binding. HLH is a protein structural motif that defines one of the largest families of dimerizing transcription factors. The protein structural motif contains two α-helices, and they are connected by a loop. HTH is a protein structural motif that is capable of binding DNA. Each monomer is organized with two α-helices, and is joined by a short amino acid strand and binds to a groove in the DNA helix. So, this summarizes the difference between helix-loop-helix and helix-turn-helix.
1. “Basic helix loop helix” By I, Splette (CC BY-SA 3.0) via Commons Wikimedia
2. “HTH alignment of 3 TetR family members” By Gabbiochem – using PyMol based on PDB: 5DY0 deposited by Palanca & Rubio, PDB: 3VIB deposited by Kumaraswami, Shafer, “Brennan, and PDB: 3ZQL deposited by Le, Schumacher, Lawson, Brennan”; Buttner (CC BY 3.0) via Commons Wikimedia