Secondary structure of proteins : sheets supersecondary structure
Domains - kau.se · Domains • Smallest unit of tertiary structure • Building elements are...
Transcript of Domains - kau.se · Domains • Smallest unit of tertiary structure • Building elements are...
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Terminology
• Secondary structure • Defined by torsional angles at the alpha carbon and hydrogen bonding of the backbone. Alpha, Beta , Turns.
• Supersecondary structure or motifs • Recurring combinations of secondary structure
elements close in sequence
• Domains • Stable 3D structure formed by a continous peptide chain. Folding units.
• Mostly motifs or secondary structure.
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Illustrations of protein structure -1
Line, wireframe (Dreiding) CPK (spacefilling)
(Ribonukleas A, Weblab Viewer)
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Illustrations of protein structure- 2 -stylized representations
Lines between alfa carbons Ribbon
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Illustrations of protein structure - 3
Ribbon for beta strands och cylinders of for alfa helices
Accessible surface (colored according to charge)
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Connection of antiparallel β-strands
β-meander Greek key β-hairpin (hårnål)
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Greek key from extended harpin
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α-hairpin
short loops with 2-4 residues connection two nearly antiparallel alpha helices
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Figurer efter Jon Cooper, PPS
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Helix-turn-helix motif Approx. perpendicular alpha helixes connected by short loop. Common in DNA binding
Petsko& Ringe Fig 150
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EF-hand
se även Bränden &Tooze 2.13
Calcium binding loop with carboxylate side chains
Ca Asp Asp
Asp
Calcium binding proteins, e.g. calmodulin
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Crossover in parallel β-structures
All observed crossovers are right-handed; probably related to twist
β-x-β-unit (chiral)
Petsko&Ringe fig. 1.60
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β-α-β motif
α-helix as crossover, parallel with the strands
α
β β
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Zinc fingers Domain structure containing alpha helix+beta hairpin, coordination of zinc by his and cys residues contribute to stability
DNA-binding proteins often contain several Zn-finger domains
Petsko&Ringe fig 1.49
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Domains/Folds Domains
• Smallest unit of tertiary structure
• Building elements are secondary structures and/or supersecondary structures
• Continuous peptide chain, independent folding unit • Proteins contain one or several domains
• Domains are sometimes functional units
• Tertiary structure includes structures of domains and domain interfaces.
• Quarternary structure includes subunit interfaces; similar to domain interfaces
14 A limited number of folds?
Statistik från PDB (2010)
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Domain structure
• Architecture
Secondary structure and motifs, their orientation and packing
• Topology
The ordering of secondary structure elements in the amino acid sequence A given architecture can be realized with different topologies
Example: antiparallellt 4-stranded β-sheet is an architecture that can be a beta meander or a Greek key
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Topology diagrams Beta structure
One domain of aspartate transcarbamylas Flavodoxin plastocyanin
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TOPS topology diagrams
Cu/Zn superoxide dismutase
Topologidiagram i TOPS
helix (alfa eller 3.10)
betasträng
Topology databaseTOPS
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The major domain types
• Alpha helix domains Mainly alpha helix (CATH:>60% alpha and <5% beta . >50% alpha-alpha and <5% beta-beta contacts )
• Beta-sheet domains antiparallella beta sheetl (CATH:<5% alpha and >50% beta . <10% alpha-alpha and >50% beta-beta contacts
• Alpha beta domains • Alpha /beta domains
Beta-alpha-beta motifs ; parallel beta structure • Alpha+beta domains
Some alfahelix, some beta sheet (antiparallel) with helix-sheet packing
• Small irregular domains Disulphides, metal ions with structural function
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19 A universe of proteins
Alpha- ness
Alpha/ Beta- ness
Beta- ness
Factor analysis of structural differences:
• Most of the variability described by 3 factors
• Can be transformed into variables alpha, beta and alpha/beta.
• 3-dimensional fold space
• Size increases with distance from origo
Genomics&Proteomics vol 4,p. 22; Hou et al, PNAS vol 100 p. 2386
20 Statistics from CATH database for fold classification
1. Alpha
2. Beta 3. Alpha Beta
4. Few secondary structure
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Alpha helix proteins/domains
• Lone helix Peptide hormones (glucagon); domains in larger proteins
• Coiled coils, leucine zippers • 4-helix bundles
Several topologies • Globin like
Heme binding Phycocyanins
• Folds containing DNA-binding helix-turn-helix motifs
• Long alfa hairpins (t superhelix) • EF-hand • Alfa horseshoe, alfa solenoid, alfa/alfa-barrel
CATH: five architectures, ortogonal bundle (bunt), up-down bundle och nonbundle , horseshoe alfa solenoid, alfa/alfa-barrel
SCOP: 144 different folds with alfa helix only Some interesting groups:
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Side chain packing: basics
Geometric packing density: Ratio between the volume included by the av van der Waals surfaceand the volumee occupied by the molecule or aggregate. Maximal packing of spheres 0.74 Organic crystals: 0.70-0.78 Oils, glasses < 0.70 Proteins: 0.68-0.82 compressibility: k(oil)/k(protein) ≈ 20 About 25% the volume unoccupied; mainly small cavities. Larger cavities can be filled with water av
Cut-away view of protein interior
Petsko&Ringe fig 1.27
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Coiled coil
• Two amphiphilic α-helixes held together by hydrophobic interaction
• Primary structure: Repeated sequence of 7 aa’s where residues 1 och 4 are hydrophic and residues 5 and 7 hydrophilic. ”Heptad repeat”
figur efter Antti Iivanainen, PPS
1 4
1 4
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The hydrophic surface is helical
Straightening the hydrophobic surface produces left-handed superhelixes
sidechains 1,4,8,11,15,18 green
Also complementary surfaces (“knobs into holes “)
See also figs 1.67, 1.68 in Petsko&Ringe
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Packing of α-helixes: the ridges and grooves model
±4n; 26o vinkel med axeln ±n; ca 80o
vinkel med axeln
±3n; ca 45o vinkel med axeln
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4 5
8 9
12 11
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12 11
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Figurer efter Jon Cooper, PPS
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4n ridges and 4n grooves produces ca 50o angle 26 + 26 =52o
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4n ridges and 3n grooves produces ca 20o angle
4n; 26o 3n; 45o
ca 20o
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Observed helix-helix contact angles
Ω
Soluble proteins
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4-helix-bundle proteins: architecture
4 helices ; ca 20 degree angles
Petsko&Ringe fig 1.54
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Side chain distribution
• Hydrophobic side chains (green) form a hydrophobic core, hydrophilic side chains om the outside (cytokrom b562 from top)
jfr Bränden & Tooze, fig 3.2
Binding site for prostethic groups (heme in this case) sandwiched between helixes
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4-helix-bundles: topologies
• Up-and down (eg cyt b562, myohemyrytrin) • Single cross-over (ferritin,
ribonukleotidreduktas; both with 2 Fe)
• Two crossovers; cytokines (hormoner, e. g. interleukin)
Petsko&Ringe fig 1.28,1.51, 1.54
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Globin-like proteins
Architecture: 8 alpha helixes (A-H) with contact angle 20, 50 and 90 degrees . Contains heme or phtosynthetic pigment Supersecondary structure: helixes G och H in alpha hairpin
A
B
C
D
E F
G
H
heme
Myoglobin
• Heme-containing • Phycocyanins
Petsko&Ringe fig 1.55
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Helix-helix packing in globins
Helixes G och H constitute helix hairpin 20 deg. angle
Other helix-helixcontacts:
• ca 50 deg (B-G; F-H)
B G
F
H
G
H
• Ca 90 deg! (E-B, E-G) Glycine residues.
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Sequence-strucure correlation in globins? 12 different proteins with globin fold known (SCOP, 1998 [81 proteins 2010]),
• Different sequences (only 16 % simlarity between the most distant) but same fold.
• Common feature: hydrophobic interior (helix-helix and helix-heme contacts), hydrophilic exterior
Backbone grey Hydrophobic green Hydrphilic blue heme red
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Alpha horsehoe
PDB: 1lrv
Also Armadillo repeat (ARM) interaction domain ; see Petsko& Ringe fig 3.2
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Alpha solenoid
Containing lipids and pigments
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Alpha/alpha barrel
(barrel) Top view Side view
Pdb-file: 1cem. Cellulase from Clostridium thermocellum