Structural Motifs: Super-secondary structures

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

1. Helix-turn-helix

2. Helix-loop-helix

3. Helix-hairpin-helix

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

1. Beta-alpha-beta

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

structure.

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

hydrogen bonds.

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.

Helix-turn-helix

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

transcription itself.

lambda Cro

Helix-loop-helix

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

exonucleases.

Helix-hairpin-helix

Alpha-alpha corner

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.

EF hand

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

Myosin walks down an actin filament

Bovine trypsin inhibitor Snake venom erabutoxin

Beta hairpin

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.

Beta-beta corner

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.

Staphylococcus nuclease

Long insertion between strands 3 and 4

Gamma crystallin

• 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

evolutionarily conserved,

whereas the second loop

rarely has a known function

Helix above the plane Helix below the plane

Right-handed> 95%

Left-handed

The rationale for this handedness is not clear

Beta-alpha-beta motif

Rossmann Fold

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.

nucleotidebinding site

β-meander motif

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.

Psi-loop motif

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,

“Positive-inside rule”

• Examples: Cell surface receptors, Ion

channels, Active and passive transporters

Transmembrane Motifs: Helix bundles

Transmembrane Motifs: Beta barrels

• Anti-parallel sheets rolled into cylinder

• Examples: Outer membrane of Gram negative bacteria, Porins (passive, selective diffusion)

Probably one of the most widespread type of protein folds, the strands of the beta-sheet are

also connected by helices:

TIM barrel fold

Database of Structural motifs in Proteins

http://www.203.200.217.185/DSMPO/