BT631-6-structural_motifs

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BT631-6-structural_motifs

  1. 1. Structural Motifs: Super-secondary structures
  2. 2. 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
  3. 3. 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.
  4. 4. 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?
  5. 5. 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
  6. 6. 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
  7. 7. 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.
  8. 8. 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
  9. 9. Alpha-alpha corner Short loop regions connecting helices which are roughly perpendicular to one another are referred to as alpha-alpha-corners.
  10. 10. 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
  11. 11. 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
  12. 12. Myosin walks down an actin filament
  13. 13. 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.
  14. 14. 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
  15. 15. 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.
  16. 16. 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.
  17. 17. 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
  18. 18. 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. nucleotide binding site
  19. 19. 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.
  20. 20. 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.
  21. 21. 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.
  22. 22. • 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
  23. 23. Transmembrane Motifs: Beta barrels • Anti-parallel sheets rolled into cylinder • Examples: Outer membrane of Gram negative bacteria, Porins (passive, selective diffusion)
  24. 24. Probably one of the most widespread type of protein folds, the strands of the beta-sheet are also connected by helices: TIM barrel fold
  25. 25. Database of Structural motifs in Proteins http://www.203.200.217.185/DSMPO/

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