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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 - 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 globular protein domain 1 domain 2 fold stack
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
Hemo- globin Hemo- globin Homologous proteins have similar folds. True, but trivial. NON-trivial: Many NON-homologous proteins have similar folds.
-sheets: usually, twisted (usually, right-) -proteins ____ H-bonds: within sheets Hydrophobics: between sheets
sandwiches & cylinders Orthogonal packing Aligned packing of -sheets of -sheets
Retinol-binding protein orthogonal packing of one rolled -sheet
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
2 5 Greek key 2::5 Greek key 3::6 4 7 6 3 non-crossed loops 1 IG-fold:aligned packing of -sheets
-sandwich Greek key: edge of sandwich Interlocked pairs: center of sandwich Hydrophobic surfaces of sheets of the sandwich
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
aligned packing of -sheets 6-bladed propeller neuraminidase
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!)
-proteins H-bonds: within helices & Hydrophobics: between helices
Quasi-cylindrical core (in fibrous) Quasi-flat core Quasi-spherical core MOST COMMON
Orthogonal packingSimilar to orthogonal of LONG -helicespackingof -sheets
Aligned packingSimilar to aligned of LONG -helicespackingof -sheets
Quasi- spherical core: MOST COMMON Quasi-spherical polyhedra no loop turns of ~360o no loop crossings
CLOSE PACKING Packing of ridges: “0-4” & “0-4”: -500 “0-4” & “1-4”: +200 -600 -500 +600 +200 IDEAL POLYHEDRA * *
/ proteins H-bonds: within helices & sheets Hydrophobics: between helices & sheets
Regular secondary structure sequence: b -a - b -a - b -a - b -a - b - ... aand b layers right-handed superhelices
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
+ proteins H-bonds: within helices & sheets Hydrophobics: between helices & sheets
+: a) A kind of regularity in the secondary structure sequence: b -a - b - b -a - b ... Ferridoxin fold
+: 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”)
TYPICAL FOLDING PATTERNS J.Richardson, 1977
EMPIRICAL RULES separateaand b layers right-handed superhelices Lost H-bonds: defect! no large, ~360o turns no loop crossings NO ‘defects’
RESULT: NARROW SET OF PREDOMINANT FOLDING PATTERNS these are those that have no ‘defects’
C A T H S C O P Globular domains
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
e.g.: Unusual fold (noa, almost nobstructure: bad for stability) - BUT: very special sequence (very many Cysteins, and therefore very many S-S bonds)
Unusual fold (GFP): helix inside Usual folds: helices outside
What is more usual: sequence providingainside orb binside? a b b N>150
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Small protein details Example: Miller, Janin, Chothia 1984
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
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
“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.
RATIONAL STRUCTURAL CLASSIFICATION OF PROTEINS Globular domains C A T H S C O P
- Structures of water-soluble globular proteins - Physical selection of protein structures: min. of defects! - Rational structural classification of proteins