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CH339K

CH339K. Proteins: Higher Order Structure. Higher Levels of Protein Structure. Side chains hang off the backbone. Repetitive background: -N-C-C-N-C-C-.

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CH339K

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  1. CH339K Proteins: Higher Order Structure

  2. Higher Levels of Protein Structure

  3. Side chains hang off the backbone Repetitive background: -N-C-C-N-C-C-

  4. The shape of the peptide chain can be defined by the three consecutive bond torsional anglesBond Rotation Torsion angle definedNH to Ca free phi Ca to C=O free psiC=O to NH rigid planaromega

  5. Since w is constrained, only f and y can vary There are steric restrictions on what values they can assume

  6. Permissable F-Y Angles(Ramachandran Plot)

  7. Secondary Structures • Represent interactions among backbone atoms • Examples • a-helices • Other helices • b-sheets • b- and g-turns • These structures have characteristicfandyangles

  8. a-helix Pauling, Corey, and Branson (1951) H bonds between • carbonyl O of residue n • amide H of residue n+4 Each amino acid is rotated 100o from the previous one. 3.6 amino acids per turn

  9. R/V Alpha Helix Woods Hole Oceanographic Institute 1966-2011

  10. Helical parameters – Pitch and Rise

  11. Backbone forms helix Side chains extend outwards f ≈ -57o • ≈ -47o 3.6 residues/turn

  12. Helix Types a-helix: C=O H-bonded to NH of residue n+4 (aka 3.613 helix) 310 helix: C=O H-bonded to NH of residue n+3 • (f ≈ -49oy ≈ -26o) p-helix: C=O H-bonded to NH of residue n+5 (aka 4.116 helix) (f ≈ -57oy ≈ -80o)

  13. Helix terminologyH-bond makes a closed loop from amide H through backbone through carbonyl ODefine helix by (a) Nbr of residues per turn (e.g. 3.6 for a -helix)(b) Nbr of atoms in the loop (e.g. 13 for a -helix)

  14. Idealized Helices

  15. b-Sheets • Can be thought of as helix with two residues per helix • Backbone atoms run in a plane • Side chains extend up and down from plane • f ≈ -110o to -140o • y ≈ +110o to +135o

  16. C=O of residue n with N-H of residue n+3

  17. Gamma Turns: C=O of residue n with N-H of residue n+2

  18. F-y Angles for Secondary Structures NOTE: Left-handed a-helix has f = +57, y = +47

  19. Ramachandran Plot: Blue areas are permitted F and Y angles

  20. Ramachandran plot for pyruvate kinase

  21. Tertiary Structures • Three dimensional folding • Determined by side chaininteractions • Salt links • H-Bonds • Disulfides • Hydrophobic interactions • Fibrous Proteins • Globular Proteins

  22. Fibrous Proteins Keratin a-keratin: hair, horns, and hoofs of mammals b-keratin: scales, claws and shells of reptiles, beaks and claws of birds, porcupine quills

  23. a-keratin • Lots of Ala, Gly, Cys • All a-helix (well, almost) Right handed Left handed

  24. Disulfides in the Barber Shop Sodium thioglycolate Various peroxides

  25. Fibrous Proteins - Fibroin 75-80% Ala/Gly 15% Ser

  26. Within a fiber: crystalline regions are separated by amorphous regions.

  27. Fibrous Proteins - Collagen Left handed helix of tropocollagen forms right handed triple helix of collagen.

  28. Hydroxyproline participates in H-bonding between tropocollagen chains

  29. (1) (2) In the absence of vitamin C, reaction 2 oxidizes Fe2+ to Fe3+.

  30. Lack of hydroxyls causes serious destabilization of the triple helix

  31. Arrrrr… Scurvy • Weakness • Paleness • Sunken eyes • Tender gums and/or tooth loss • Muscular pain • Reopening of old wounds or sores • Internal bleeding • Loss of appetite • Bruising easily • Weight loss; inability to gain weight • Diarrhea • Increased heart rate • Fever • Irritability • Aching and swelling in joints • Shortness of breath • Fatigue

  32. The Brits Found the Link Between Fruits and Veggies and Healthy Sailors Walk wide o' the Widow at Windsor, For 'alf o' Creation she owns: We 'ave bought 'er the same with the sword an' the flame, An' we've salted it down with our bones. (Poor beggars! -- it's blue with our bones!) The Widow at Windsor – Kipling We broke a King and we built a road --A court-house stands where the reg'ment goed.And the river's clean where the raw blood flowedWhen the Widow give the party.(Bugle: Ta--rara--ra-ra-rara!) The Widow’s Party - Kipling

  33. British Empire at its Peak • A healthy navy is a victorious navy (of course, my ancestors were less than thrilled…)

  34. Protein structure cartoons a-helix Antiparallel b-sheet

  35. Globular Proteins (examples)

  36. Structural Motifs – “supersecondary structures” common stable folding patterns Formed from consecutive sequences Found in proteins w/ different functions result from the physics and chemistry of the structure

  37. Greek Key Motif (antiparallel b-sheets) • Schematic of motif • Staphylococcus nuclease protein

  38. More motifs

  39. Domains – • Stable, independently folded, globular units • Common patterns found in different proteins • Typically have similar function • Caused by evolution (gene recombination / duplication) • Frequently (not always!) correspond to exons in genes Ricin B chain • Two domains • Each domain is a trefoil • 3 repeats of a sheet-loop structure • i.e. 6 repeats of a primitive fold

  40. C-rich Domain of Earthworm Mannose Receptor Fibroblast Growth Factor

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