Structural Motifs: Super-secondary structures
Super secondary structures involves the association of secondary structures in a particular
geometric arrangement. If we think of each secondary structure as a 'unit', then a super
secondary structure would be comprised of at least two 'units' of secondary structure. Some
of these super secondary structures are known to have a specific biological or structural role
but for others their role is unknown.
Helix super-secondary structures
4. Helix corner (α-α corner)
Sheet super-secondary structures
1. Beta hairpins
2. Beta corner (β-β corner)
3. Greek key motif
Mix super-secondary structures
2. Rossmann fold
Is there any difference among turns, loops and coils? How do you differentiate them?
In addition to α helices and β strands, a folded polypeptide chain contains other types of
secondary structure called turns, loops and/or coils.
Loops and turns connect α helices and β strands. The most common types cause a change in
direction of the polypeptide chain allowing it to fold back on itself to create a more compact
A turn is an element of secondary structure in proteins where the polypeptide chain reverses
its overall direction.
A coil is a region of protein structure which are generally observed to be disordered.
Loops are not well defined. A loop implies at least a few residues with no specific secondary
structure between two secondary structure elements.
They generally have hydrophilic residues and they are found on the surface of the protein.
Loops that have only 4 or 5 amino acid residues are called turns when they have internal
A hairpin is a special case of a turn, in which the direction of the protein backbone reverses
and the flanking secondary structure elements interact. A β hairpin contains a turn and two
strands - no loop.
What about a hairpin?
The helix-turn-helix (HTH) is a major structural motif observed in proteins capable of
binding DNA e.g. CAP and λ repressor (Cro).
It consists of two segments of alpha helix separated by a short irregular region, or "turn". The
one helix contributes to DNA recognition (“recognition helix”) and second helix stabilizes the
interaction between protein and DNA.
Proteins having this motifs are generally involved in cell
proliferation, establishment of DNA structure, developmental
regulation, maintenance of circadian rhythms, movement of DNA,
regulation of a myriad of bacterial operons and initiation of
A basic helix-loop-helix (bHLH) is a protein structural
motif that characterizes a family of transcription factors.
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 (CACGTG).
In general, transcription factors having HLH motif are
dimeric, each with one helix containing basic amino acid
residues that facilitate DNA binding.
Examples of transcription factors containing a bHLH
include: BMAL-1-CLOCK, C-Myc, N-Myc, MyoD,
Myf5, Pho4, HIF, ICE1, NPAS1, NPAS3, MOP5, etc.
The HhH motif is similar to, but distinct from, the helix-
turn-helix (HtH) and the helix-loop-helix (HLH) motifs.
DNA-binding proteins with a HhH structural motif are
involved in non-sequence-specific DNA binding that occurs
via the formation of hydrogen bonds between protein
backbone nitrogens and DNA phosphate groups.
What makes the Protein-DNA interaction specific?
Examples of proteins that contain a HhH motif include the
5'-exonuclease domains of prokaryotic DNA polymerases,
the eukaryotic/prokaryotic RAD2 family of 5'-3'
exonucleases such as T4 RNase H and T5, eukaryotic 5'
endonucleases such as FEN-1 (Flap) and some viral
Short loop regions connecting helices which are roughly perpendicular to one another are
referred to as alpha-alpha-corners.
EF hand is two helices connected by a loop that contains residues to coordinate calcium ion
(Ca2+). Name refers to the helices E and F in parvalbumin loop.
Proteins of this type form homo- or heterodimers. Two alpha helices, one from each monomer,
form a coiled-coil structure at one end due to interactions between leucines that extend from
one side of each helix. Beyond the dimerization interface the alpha helices diverge, allowing
them to fit into the major groove of the DNA double helix. The dimerization partner
determines DNA binding affinity and specificity.
Stability is achieved by efficiently burying the hydrophobic residues. Found in fibrinogen
(essential in blood coagulation), DNA binding protein (GCN4, AP1), structural proteins
(spectrin), muscle protein myosin.
Leucine Zipper Motif
Bovine trypsin inhibitor Snake venom erabutoxin
The β hairpin (also called β ribbon or β-β unit) is a simple protein structural motif involving
two beta strands that look like a hairpin. The motif consists of two strands that are adjacent in
primary structure, oriented in an anti-parallel direction and linked by a short loop of two to
five amino acids.
Beta-hairpins can be formed from isolated short peptides in aqueous solution, suggesting that
hairpins could form nucleation sites for protein folding.
A beta-beta-corner can be represented as a long beta-beta-hairpin folded orthogonally on itself
so that the strands, when passing from one layer to the other, rotate in a right-handed direction
about an imaginary axis.
Greek Key Motif
The Greek key motif consists of four adjacent antiparallel strands and their linking loops. It
consists of three antiparallel strands connected by hairpins, while the fourth is adjacent to the
first and linked to the third by a longer loop. This type of structure forms easily during the
protein folding process.
Examples of proteins having Greek Key Motif: Prealbumin, PapD (which is a chaperon),
Nitrite reductase, Insecticidal δ-endotoxin, Bacterial cellulase, Spherical virus capsid proteins.
Long insertion between strands 3 and 4
• Changing protein
concentration gradient across
the lens results in a smooth
gradient of the refractive
index for visible light that is
crucial for vision.
Beta-alpha-beta (βαβ) motif allows two parallel beta strands
– There is a long crossover between the end of the first strand and the beginning of the
second strand frequently made by a helix
First loop is often
whereas the second loop
rarely has a known function
Helix above the plane Helix below the plane
The rationale for this handedness is not clear
Simple motifs can combine to generate more complex structures e.g. Rossman fold (=2xβαβ
motif with the middle β shared between the two units) binds nucleotides.
A simple super secondary protein topology composed of 2 or more consecutive anti-parallel
β-strands linked together by hairpin loops. This motif is common in β-sheets and can be found
in several structural architectures including β-barrels and β-propellers.
The Ψ-loop motif consists of two anti-parallel strands with one strand in between that is
connected to both by hydrogen bonds. There are four possible strand topologies for single Ψ-
loops. This motif is rare as the process resulting in its formation seems unlikely to occur
during protein folding. The Ψ-loop was first identified in the aspartic protease family.
Zinc Finger Motif
It consists of a segment of alpha helix bound to a loop by a zinc ion. The zinc ion is held in
place by two cysteine and two histidine R groups. The alpha helix lies in the major groove of
the DNA double helix. Zinc finger motifs are often repeated in clusters.
• Long stretches of apolar amino acids, fold
into transmembrane alpha-helices,
• Examples: Cell surface receptors, Ion
channels, Active and passive transporters
Transmembrane Motifs: Helix bundles