Supersecondary structures or motifs, are simple and frequent combinations of the secondary structure with a specific geometric arrangement. Supersecondary structures can also be considered as an intermediate between secondary and tertiary structures.
Some of these motifs are associated with a particular defined function (e.g. DNA binding), and others can be the part of larger structural assemblies. The term ‘motif’ is also describes a consensus sequence of amino acids, i.e. a partial sequence common to a number of different proteins, which may or may not adopt similar conformations in the different proteins. The some of the simplest motifs are described below:-
Supersecondary structures of proteins or motifs
Table of Contents
- Supersecondary structures of proteins or motifs
- Apha helix (Supersecondary structures or motifs)
- Beta Sheet (Supersecondary structures or motifs)
- Alpha-Beta combination supersecondary structures or motifs
- Some common supersecondary structure or motifs
Apha helix (Supersecondary structures or motifs)
Helix turn helix (HTH)
- Helix-turn-helix (HTH) consists of two α-helices that constitutes of a right-handed three helical bundle with helices α2 and α3 arranged perpendicular to one another joined by a short strand of amino acids (figure below).
- α3 is recognition helix that binds to DNA major groove through a series of hydrogen bonds and various Vander wall forces with exposed bases.
- The protein–DNA interaction is stabilized by nonspecific contacts between the DNA backbone and residues in α2 and the turn between α2 and α3.
- These helix-turn-helix structure found in many proteins(transcription factors).
Helix turn helix motif function
- Its major function is in DNA recognition, as α3 helix is involved in the recognition and is known as “recognization helix” while another one stabilizes the interaction between DNA and Protein.
- Helix-turn-helix motif are involved in many processes that includes DNA repair, RNA metabolism, and protein-protein interaction.
Helix turn helix (HTH) example
- Large number of prokaryotic repressors belong to the helix-turn-helix family of proteins. like λ repressor with its cognate operator, OL1.
- Prokaryotic regulatory proteins such as Cro, CAP, and λ repressors
Helix loop helix (HLH)
- Helix loop helix are eukaryotic homolog of the HTH motif and are characterized by two ampipathic α-helices (60–90 amino acids) connected by a loop (10-25 amino acids).
- The eukaryotic HLH is physically larger than the prokaryotic counterpart HTH motif.
- Unlike HTH proteins, the actual DNA-binding motif of the HLH proteins is a stretch of about 13 “basic” amino acids adjacent to the HLH whose main role is in protein dimerization.
- Therefore, entire motif comprising the DNA-binding basic region and the HLH is termed bHLH. The two amphipathic helices, particularly the highly conserved hydrophobic amino acids, are thought to mediate dimerization, which is a prerequisite to DNA binding.
- In general, transcription factors including this domain are dimeric, each with one helix that contains basic amino acid residues facilitate DNA binding.
- Most often, one helix is smaller in bHLH, and, because of the flexibility of the loop, helps in dimerization by folding and packing against another helix.
- bHLH motif typically binds to a consensus sequence called E-box (CACGTG).
Helix turn helix (HTH) example
- BMAL-1- CLOCK
The calcium binding motif (EF-hand)
- The motif comprises two α helices, E and F that flank a loop of 12 contiguous residues. It appears much like the spread thumb and forefinger of the human hand,
- Five of the loop residues should contain an oxygen atom and preferably be aspartate or glutamate, as they act as calcium ligands (Figure below).
- Residue 6 of the loop must be a glycine because the side chain of any other residue would disturb the structure of the motif. Finally, a number of side chains form a hydrophobic core between the α helices and thus must be hydrophobic.
- Usually binds calcium ion
- Example-appear in each structural domain of the signalling protein calmodulin and in the muscle protein troponin-C.
Leucine zipper motif
- One of the most common three-dimensional supersecondary structures or motifs in proteins
- The basic region-leucine zipper motif (bZIP) consist of a long helix, composed of two subunits
- Basic region– present immediately N-terminal to leucine zipper => bZIP.
- Amphipathic α-helix – consists of hydrophobic region due to leucine and hydrophilic amino acids outside. α-helix have leucine every 7th residue. This hydrophobic region provides an area for dimerization, allowing the motifs to “zip” together. Furthermore, the hydrophobic leucine region is absolutely required for DNA binding.
- Leucine zipper motifs are usually found as part of a DNA-binding domain in many transcription factors, and are therefore these motifs are involved in regulating gene expression.
- Leucine zippers are found in both eukaryotic and prokaryotic regulatory proteins, but are mainly a feature of eukaryotes.
The bZIP family of transcription factors consists of a basic region that interacts with the major groove of a DNA molecule through hydrogen bonding, and a hydrophobic leucine zipper region that is responsible for dimerization.
Beta Sheet (Supersecondary structures or motifs)
- β-Hairpins are supersecondary structures or motifs formed by two antiparallel β-sheet strands joined with only 2–5 intervening residues forming a turn between them.
Greek key motif
- The Greek key motif is found in anti-parallel sheets with four adjacent β- strands.
- This greek key supersecondary structures or motifs forms easily during the protein folding process.
- Sperical virus capsid proteins
- Insecticidal δ-endotoxin
- Bacterial cellulase
- PapD (which is a chaperon)
- Nitrite reductase
- Antiparallel β sheets are linked sequentially by short loops or hairpins consisting of two, three or four residues.
- Basic antiparallel β pleated sheet.
Alpha-Beta combination supersecondary structures or motifs
- The motif that is formed is a β strand followed by a loop of an α helix, then another loop, and, finally, the second β strand.
- The loop connecting the carboxy end of the β strand with the amino end of the α helix often have conserved amino acid sequences in homologous proteins and are involved in forming the active site of these structures.
- Proteins containing beta-sheets are made up of these types of motifs. The loops that connect both strands are involved in ligand binding and motif is found in ion channels.
- Zinc finger supersecondary structuresor motifs consists of an α helix and two short antiparallel β strands that are held together by a zinc ion, which form coordinate bond with side- chain in the polypeptide.
- There are a number of types of zinc fingers, each with a unique three-dimensional architecture (classified into several different structural families).
- Cys2His2 –> Two ligands from a knuckle and two more from the c terminus of a helix
- Gag knuckle –> Two ligands from a knuckle and two more from a short helix or loop.
- Treble clef –> Two ligands from a knuckle and two more from the N-terminus of a helix.
- Zinc ribbon –> Two ligands each from two knuckles.
- Zn2/Cys6 –> Two ligands from the N terminus of a helix and two more from a loop.
- TAZ2 domain like –>Two ligands from the termini of two helices.
- X fin (Xenopus DNA binding protein with a role in embryogenesis).
- CysCysHisCys (C2HC) type zinc finger domain found in eukaryotes. Proteins containing these domains include–>MYST family HAT, Myt1, Suppressor of tumourigenicity protein 18 (ST18).
Some common supersecondary structure or motifs
A common supersecondary structure or motifs consists of antiparallel β sheets are linked sequentially by short loops or hairpins consisting of two, three or four residues
Two or more α helices are wrapped around each other to form left handed supercoil. Strips of hydrophobic side-chains along the length of each helix interact with each other.
Example:- Myosin (a motor protein); α- keratin (a structural protein, e.g. in skin and hair)