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PROTEIN PHYSICS LECTURE 13-16

PROTEIN PHYSICS LECTURE 13-16. - Structures of water-soluble globular proteins - Physical selection of protein structures - Structural classification of proteins. Globular proteins (water-soluble). Membrane. Fibrous. H-bonds & hydrophobics. ____.  single- domain

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PROTEIN PHYSICS LECTURE 13-16

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  1. PROTEIN PHYSICS LECTURE 13-16 - Structures of water-soluble globular proteins - Physical selection of protein structures - Structural classification of proteins

  2. Globular proteins (water-soluble) Membrane Fibrous H-bonds & hydrophobics ____

  3.  single-domain globular protein domain 1 domain 2 fold stack

  4. X-RAY One protein, various crystallizations NMR Structures, compatible with one NMR experiment Homologous (closely related) proteins Secondary structures (a-helices, b-strands) are the most rigid and conserved details of proteins; they are determined with the smallest errors and form a basis of protein classification

  5. Hemo- globin Hemo- globin Homologous proteins have similar folds. True, but trivial. NON-trivial: Many NON-homologous proteins have similar folds.

  6. -sheets: usually, twisted (usually, right-)  -proteins ____ H-bonds: within sheets Hydrophobics: between sheets

  7. sandwiches & cylinders Orthogonal packing Aligned packing of -sheets of -sheets

  8. Retinol-binding protein orthogonal packing of one rolled -sheet

  9. 5 5 4 4 2’ 3 5’ 6 5’ 3 2’ 6 1 1 2 2 Trypsin-like SER-protease Acid-protease orthogonal packings of -sheets

  10. 2 5 Greek key 2::5 Greek key 3::6 4 7 6 3 non-crossed loops 1 IG-fold:aligned packing of -sheets

  11. -sandwich Greek key: edge of sandwich Interlocked pairs: center of sandwich Hydrophobic surfaces of sheets of the sandwich

  12. 1 2 2 6 6 3 5 8 6 1 8 1 3 3 8 g-crystallin bCAB cpSTNV aligned packings of -sheets a) different: only topologies b) equal: even topology

  13. aligned packing of -sheets 6-bladed propeller neuraminidase

  14. Left-handed -prism:Acyl transferase Right-handed -prism:Pectate lyase ___________________________________________ TOPOLOGY of chain turns between parallel -strands UNusual LEFT-HANDED chain turns (AND NO b-TWIST!) Usual RIGHT-HANDED chain turns (AND RIGHT b-TWIST!)

  15. -proteins H-bonds: within helices & Hydrophobics: between helices

  16. Quasi-cylindrical core (in fibrous) Quasi-flat core Quasi-spherical core MOST COMMON

  17. Orthogonal packingSimilar to orthogonal of LONG -helicespackingof -sheets

  18. Aligned packingSimilar to aligned of LONG -helicespackingof -sheets

  19. Quasi- spherical core: MOST COMMON Quasi-spherical polyhedra no loop turns of ~360o no loop crossings

  20. CLOSE PACKING Packing of ridges: “0-4” & “0-4”: -500 “0-4” & “1-4”: +200 -600  -500 +600  +200 IDEAL POLYHEDRA * *

  21. / proteins H-bonds: within helices & sheets Hydrophobics: between helices & sheets

  22. TIM barrel Rossmann fold

  23. Regular secondary structure sequence: b -a - b -a - b -a - b -a - b - ... aand b layers right-handed superhelices

  24. Classification of b-barrels: “share number” S and strand number N. Here: S=8, N=8 Standard active site position is given by the archi- tecture N N N N

  25. + proteins H-bonds: within helices & sheets Hydrophobics: between helices & sheets

  26. +: a) A kind of regularity in the secondary structure sequence: b -a - b - b -a - b ... Ferridoxin fold

  27. +: b) Secondary structure sequence: composed of irregular blocks, e.g.: b - b - b - b - b -a - b - b -a -a ... 1 4 5 OB-fold of the b-subdomain of nuclease 3 2 1’ Nuclease fold (“Russian doll effect”)

  28. TYPICAL FOLDING PATTERNS J.Richardson, 1977

  29. EMPIRICAL RULES separateaand b layers right-handed superhelices Lost H-bonds: defect! no large, ~360o turns no loop crossings NO ‘defects’

  30. RESULT: NARROW SET OF PREDOMINANT FOLDING PATTERNS these are those that have no ‘defects’

  31. C A T H  S C O P Globular domains

  32. Efimov’s “trees”

  33. 80/20 LAW:

  34. EMPIRICAL RULES for FREQUENT FOLDS aand bstructures, right-handed separate a and b layers superhelices Lost H-bonds: defect! no loop crossing no large (360-degree) turns

  35. e.g.: Unusual fold (noa, almost nobstructure: bad for stability) - BUT: very special sequence (very many Cysteins, and therefore very many S-S bonds)

  36. Unusual fold (GFP): helix inside Usual folds: helices outside

  37. What is more usual: sequence providingainside orb binside? a b b N>150

  38. ____ _____

  39. Small protein details Example: Miller, Janin, Chothia 1984

  40. WHAT IS “TEMPERATURE”? THEORY Closed system: energy E = const S ~ln[M] CONSIDER: 1 state of “small part” with  & all states of thermostat with E-. M(E-) = 1•Mth(E-) St(E-) = k •ln[Mt(E-)]  St(E) - •(dSt/dE)|E Mt(E-) = exp[St(E)/k] • exp[-•(dSt/dE)|E/k] Thus: d[ln(Mt)]/dE = 1/kT

  41. Protein structure is stable, if its free energy is below some threshold For example: below that of completely unfolded chain; or: below that of any other globular structure

  42. “Multitude principle” for physical selection of folds of globular proteins (now: “designability”): the more sequences fit the given architecture without destroying its stability, the higher the occurrence of this architecture in natural proteins.

  43. RATIONAL STRUCTURAL CLASSIFICATION OF PROTEINS Globular domains C A T H  S C O P

  44. - Structures of water-soluble globular proteins - Physical selection of protein structures: min. of defects! - Rational structural classification of proteins

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