Secondary structure of proteins: turns and helices

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Secondary structure of proteins turns and
helices
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Levels of protein structure organization
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Peptide bond geometry
Hybrid of two canonical structures
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Electronic structure of peptide bond
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Peptide bond planarity

• The partially double character of the peptide
  bond results in
• planarity of peptide groups
• their relatively large dipole moment

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Side chain conformations the c angles
c1
c2
c3
c10
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Dihedrals with which to describe polypeptide
geometry
side chain
main chain
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Peptide group cis-trans isomerization
Skan z wykresem energii
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Because of peptide group planarity, main chain
conformation is effectively defined by the f and
y angles.
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Side chain conformations
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The dihedral angles with which to describe the
geometry of disulfide bridges
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Some ? and ? pairs are not allowed due to steric
overlap (e.g, ??0o)
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The Ramachandran map
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Conformations of a terminally-blocked amino-acid
residue
E
Zimmerman, Pottle, Nemethy, Scheraga,
Macromolecules, 10, 1-9 (1977)
C7eq
C7ax
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Energy maps of Ac-Ala-NHMe and Ac-Gly-AHMe
obtained with the ECEPP/2 force field
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Energy curve of Ac-Pro-NHMe obtained with the
ECEPP/2 force field
fL-Pro-68o
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Energy minima of therminally-blocked alanine with
the ECEPP/2 force field
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Elements of protein secondary structure

• Turns (local)
• Loops (local)
• Helices (periodic)
• Sheets (periodic)
• Statistical coil (not regular)

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g- and b-turns
g-turn (fi1-79o, yi169o)
b-turns
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Types of b-turns in proteins
Hutchinson and Thornton, Protein Sci., 3,
2207-2216 (1994)
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Older classification
Lewis, Momany, Scheraga, Biochim. Biophys. Acta,
303, 211-229 (1973)
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fi1-60o, yi1-30o, fi2-90o, yi20o
fi160o, yi130o, fi290o, yi20o
fi1-60o, yi1-30o, fi2-60o, yi2-30o
fi160o, yi130o, fi260o, yi230o
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fi1-60o, yi1120o, fi280o, yi10o
fi160o, yi1-120o, fi2-80o, yi10o
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fi1-80o, yi180o, fi280o, yi2-80o
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cis-proline
yi180o, fi2lt60o yi160o, fi2180o
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Helical structures a-helical structure predicted
by L. Pauling the name was given after
classification of X-ray diagrams.
Helices do have handedness.
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Geometrical parameters of helices
Average parameters of helical structures
H-bond
Turns closed by H-bond
radius
Type
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Idealized hydrogen-bonded helical structures
310-helix (left), a-helix (middle), p-helix
(right)
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a-helices deformationsbifurcated or mismatched
H-bonds disrupt periodic structure
1,6-hydrogen bonds at helix ends.
Bifurcated hydrogen bonds (1,4 and 1,5) at helix
ends.
1,3-, and 1,4-hydrogen bonds at helix ends.
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Znieksztalcenia a-helisdodatkowe wiazania
wodorowe na koncachhelis (wiazanie wodorowe
rozwidlonelub zmiana wiazania wodorowego)
Bifurcated hydrogen bonds (1,4 and 1,5) at the
N-terminums of helix A of thermolysin.
Bifurcated hydrogen bonds (1,4 and 1,5) at the
C-terminums of helix D of carboxypeptidase.
1,6 and 2,5 hydrogen bonds at the C-terminus of
helix A in lysosyme
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Helix deformation (kink)
Example from myoglobin structure. The kink angle
is up to 20o
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Additional H-bonds with water molecules
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Other factors resulting in helix deformation

1. Deformation is forced because of tertiary
   structure (crowding).
2. Strong H-bonding (e.g., between side chains).
3. Helix breakers inside Pro will result in a kink
   for sure and Gly almost always but small polar
   amino acids such as Ser and Thr also can.

Kink inside an a-helix in phosphoglyceryl
aldehyde dehydrogenase
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Helix breaking by Pro residues
Ring constraint
No amide hydrogen
O
C-O
N
H
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Helix capping
Izolowana 12-resztowa a-helisa posiada 12 grup
donorowych NH oraz 12 grup akceptorowych CO
wiazania wodorowego (w obrebie lancucha
glównego). W 12 resztowej helisie moze utworzyc
sie tylko 8 wewnatrzczasteczkowych wiazan
wodorowych. N- i C-Koncowy fragment helisy
zawiera wiec 4 wolne donory NH i 4 wolne
akceptory CO wiazan wodorowych. Kompensacja tej
niedogodnosci jest wystepowanie polarnych reszt
aa na N- i C-koncu helisy. N- i C-Koncowe
fragmenty helis wykazuja dodatkowo rózne
preferencje co do okreslonych reszt aa.
Residue preferences to occur at end or
close-to-end positions
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a-helices always have a large dipole moment
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Side chain arrangement in helices
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Contact interactions occur between the side
chains separated by 3 residues in amino-acid
sequence
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Schematic representation a-helices helical wheel
3.6 residues per turn a residue every 100o.
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Examples of helical wheels
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Amphipatic (or amphiphilic) helices
One side contains hydrophobic amino-acids, the
other one hydrophilic ones. In globular
proteins, the hydrophilic side is exposed to the
solvent and the hydrophobic side is packed
against the inside of the globule
Hydrophobic
Hydrophilic
Amphipatic helices often interact with lipid
membranes
hydrophilic head group
aliphatic carbon chain
lipid bilayer
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download cytochrome B562
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Length of a-helices in proteins
10-17 amino acids on average (3-5 turns) however
much longer helices occur in muscle proteins
(myosin, actin)
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Proline helices (without H-bonds)
Polyproline helices I, II, and III (PI, PII, and
PIII) contain proline and glycine residues and
are left-handed. PII is the building block of
collagen has also been postulated as the
conformation of polypeptide chains at initial
folding stages.
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Polyproline ring conformations
C2 (half-chair) conformations of Cg-endo
L-proline CS (envelope) conformation of Cg-endo
L-proline peptide group at the trans position
with respect to Ca-H (Y120o), as in
collagene CS (envelope) of Cg-egzo L-proline
with the peptide group at the cis orientation
with respect to Ca-H (Y-60o)

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f and y angles of regular and polyproline helices

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Deca-glycine in PPII and PPI without hydrogen
atoms, spacefill modells, CPK colouring
Poly-L-proline in PPII conformation, viewed
parallel to the helix axis, presented as sticks,
without H-atoms. (PDB)It can be seen, that the
PPII helix has a 3-fold symmetry, and every 4th
residue is in the same position (at a distance of
9.3 Å from each other).
PPI-PRO.PDB PPII-PRO.PDB

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The b-helix