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  1. 1. Beta structures
  2. 2. Beta Structures <ul><li>Functionally the most diversely populated group (antibodies, enzymes, transport proteins etc…) </li></ul><ul><li>Second biggest group of protein domain structures (after  ) </li></ul><ul><li>Built up from four to over ten beta strands </li></ul><ul><li> strands are arranged in predominantly antiparallel fashion </li></ul><ul><li>Usually two beta sheets are formed, which pack each against other, resembling barrel or distorted barrel (=double  sandwich) </li></ul>
  3. 3. Beta Structures <ul><li>Anti-parallel  strands are usually arranged in two  -sheets that pack against each other and form a distorted barrel structure, the core of the structure. </li></ul><ul><li>Depending on the way the  -strands around the barrel are connected along the polypeptide chain, they can be divided into four major groups: </li></ul><ul><ul><li>Up-and-down barrel </li></ul></ul><ul><ul><li>Greek Key barrel </li></ul></ul><ul><ul><li>Jelly roll barrel </li></ul></ul><ul><ul><li> -helix </li></ul></ul>
  4. 4. Up-and-down barrels <ul><li>Schematic and topological diagrams of an up-and-down  barrel. </li></ul><ul><li>The eight  strands are all antiparallel to each other and are connected by hairpin loops. </li></ul><ul><li>Beta strands that are adjacent in the amino acid sequence are also adjacent in the three-dimensional structure of up-and-down barrels. </li></ul>
  5. 5. Retinol-binding protein (rbp) <ul><li>The structure of human plasma retinol-binding protein (RBP) is an up-and-down  barrel. A retinol molecule, vitamin A (yellow), is bound inside the barrel, between the two  sheets, such that its only hydrophilic part (an OH tail) is at the surface of the molecule . </li></ul>
  6. 6. Retinol binding site in rbp <ul><li>Hydrophobic part fits in a hydrophobic pocket </li></ul><ul><li>Hydroxyl group exposed to solvent </li></ul>OH
  7. 7. Alterating patterns in amino acid sequence of rbp <ul><li>Amino acid sequence of  strands 2, 3, and 4 in human plasma retinol-binding protein. </li></ul><ul><li>The sequences are listed in such a way that residues which point into the barrel are aligned. </li></ul><ul><li>These hydrophobic residues are shown by arrows and are colored green. The remaining residues are exposed to the solvent. Hydrophobic amino acids are facing the core </li></ul><ul><li>Polar, charged and a few small hydrophobic are exposed to the solvent </li></ul>
  8. 8. Up-and-down barrels can contain more than 8 strands <ul><li>Porin monomer from Rhodobacter has 14  strands </li></ul>
  9. 9.  propeller in neuraminidase <ul><li>Influenza virus protein, involved in virion release from cells </li></ul><ul><li>Tetrameric protein, one monomer consists of 6 up-and down  sheets </li></ul><ul><li>Builds a propeller-like structure </li></ul>
  10. 10. Neuraminidase tetramer
  11. 11. Active site in  -propeller proteins <ul><li>On the top of propeller there are extensive loops </li></ul><ul><li>The loops form active site </li></ul>
  12. 12. Greek Key Motifs <ul><li>This motif is formed when one of the connections of four antiparallel  strands is not a hairpin connection. </li></ul><ul><li>The motif occurs when strand number n is connected to strand n + 3 (a) or n - 3 (b) instead of n + 1 or n - 1 in an eight-stranded antiparallel  sheet or barrel. The two different possible connections give two different hands of the Greek key motif. </li></ul><ul><li>In all protein structures known so far, only the hand shown in (a) has been observed. </li></ul>
  13. 13. The Fold of IgG Domains <ul><li>Beta strands labeled A-G of the constant and variable domains of immunoglobulins have the same topology and similar structures. There are two extra  strands, C' and C'' (red) in the variable domain. The loop between these strands contains the hyper-variable region CDR2. The remaining CDR regions are at the same end of the barrel in the loops connecting  strands B and C and strands F and G. </li></ul>
  14. 14. Gamma Crystallin Domain <ul><li>Found in lenses of your eyes </li></ul><ul><li>The domain structure of  -crystallin is built up from two  sheets of four antiparallel  strands, sheet 1 from  strands 1, 2, 4, and 7 and sheet 2 from strands 3, 5, 6, and 8. </li></ul><ul><li>It is obvious that the  strands are arranged in two Greek key motifs, one (red) formed by strands 1 - 4 and the other (green) by strands 5 - 8. </li></ul>
  15. 15. Complete  -crystallin Molecule <ul><li>The two domains of the complete molecule have the same topology; each is composed of two Greek key motifs that are joined by a short loop region. </li></ul><ul><li>There is a greater amino acid sequence homology between the domains than the motifs within each domain, suggesting that the four Greek Key motifs in  -crystallin are evolutionarily related by gene duplication and fusion. </li></ul>
  16. 16. Evidence for two gene duplication events in  -crystallin evolution <ul><li>Two domains have about 40% sequence identity </li></ul><ul><li>Two motifs within the domain share 20-30% sequence identity </li></ul>1. 2. x 2 x 2
  17. 17. Jelly Roll Mo tifs <ul><li>The eight  strands are drawn as arrows along two edges of a strip of paper. The strands are arranged such that strand 1 is opposite strand 8, etc.. </li></ul><ul><li>The  strands follow the surface of the barrel and the loop regions provide the connections at both ends of the barrel. </li></ul>
  18. 18. Arrangement of  strands in jelly roll barrel
  19. 19. Two Greek key motifs in jelly-roll barrel
  20. 20. Jelly-roll barrel in viruses <ul><li>Very common in subunits of spherical viruses </li></ul><ul><li>Barrel is distorted and with helices instead of some loops </li></ul><ul><li>Example: Rhinovirus (common cold) </li></ul>
  21. 21. The Globular Head of the Hemagglutinin Subunit is a Distorted Jelly Roll Structure <ul><li> strand 1 contains a long insertion, and  strand 8 contains a bulge in the corresponding position. Each of these two strands is therefore subdivided into shorter  strands. The loop region between  strands 3 and 4 contains a short  helix, which forms one side of the receptor binding site (yellow circle). </li></ul>
  22. 22. Comparison of all those  -barrels Up-and-down  -crystallin-like jelly-roll
  23. 23. Beta helix <ul><li>Two different kinds – two-sheet helix and three-sheet helix </li></ul><ul><li>Both represent deviations from idealized structure with a single spiral-like strand </li></ul>
  24. 24. Two-sheet  helix. <ul><li>The two parallel  sheets are colored green and red, the loop regions that connect the  strands are yellow. </li></ul><ul><li>Each structural unit is composed of 18 residues with 9 consensus sequence Gly-Gly-X-Gly-X-Asp-X-U-X forming a  -loop-  -loop structure, where U is a large hydrophobic residue, often Leu. </li></ul><ul><li>Each loop region contains six residues of sequence Gly-Gly-X-Gly-X-Asp where X is any residue. Calcium ions are bound to both loop regions. </li></ul>Extracellular bacterial proteinase
  25. 25. Sequence pattern in two sheet beta helix X 7 U 8 X 9 X 7 U 8 X 9 <ul><li>Gly-Gly-X-Gly-X-Asp-X-U-X </li></ul><ul><li>X=any amino acid </li></ul><ul><li>U=big hydrophobic, often Leu </li></ul><ul><li>Ca ions sit in between loops </li></ul><ul><li>Motif present in several bacterial proteases </li></ul>
  26. 26. Three-sheet  Helix <ul><li>As shown in (a), two of the  sheets (blue and yellow) are parallel to each other and are perpendicular to the third (green). In (b), each structural unit is composed of three  strands connected by three loop regions (labeled a, b and c). </li></ul><ul><li>Loop a (red) is invariably composed of only two residues, whereas the other two loop regions vary in length . </li></ul><ul><li>Unlike two-sheet beta helices, there are no repetitive sequence patterns </li></ul>