Transcript Lecture 3

SECONDARY STRUCTURE OF
PROTEINS: TURNS AND HELICES
Levels of protein structure organization
Peptide bond geometry
Hybrid of two canonical structures
60%
40%
Electronic structure of peptide bond
Peptide bond: planarity
The partially double
character of the peptide
bond results in
•planarity of peptide
groups
•their relatively large
dipole moment
Side chain conformations: the c angles
c1 c 2 c 3
c1=0
Dihedrals with which to describe polypeptide geometry
side chain
main chain
Peptide group: cis-trans isomerization
Skan z wykresem energii
Because of peptide group planarity, main chain conformation is
effectively defined by the f and y angles.
Side chain conformations
The dihedral angles with which to describe
the geometry of disulfide bridges
Some f and y pairs are not allowed due to steric
overlap (e.g, f=y=0o)
The Ramachandran map
Conformations of a terminally-blocked amino-acid residue
E
Zimmerman, Pottle, Nemethy, Scheraga,
Macromolecules, 10, 1-9 (1977)
C7eq
C7ax
Energy maps of Ac-Ala-NHMe and Ac-Gly-AHMe
obtained with the ECEPP/2 force field
Energy curve of Ac-Pro-NHMe obtained with the
ECEPP/2 force field
fL-Pro-68o
Energy minima of therminally-blocked alanine with
the ECEPP/2 force field
Elements of protein secondary
structure
•
•
•
•
•
Turns (local)
Loops (local)
Helices (periodic)
Sheets (periodic)
Statistical coil (not regular)
g- and b-turns
g-turn (fi+1=-79o, yi+1=69o)
b-turns
Types of b-turns in proteins
Hutchinson and Thornton, Protein Sci., 3, 2207-2216 (1994)
Older classification
Lewis, Momany, Scheraga, Biochim. Biophys. Acta, 303, 211-229 (1973)
fi+1=-60o, yi+1=-30o, fi+2=-90o, yi+2=0o
fi+1=-60o, yi+1=-30o, fi+2=-60o, yi+2=-30o
fi+1=60o, yi+1=30o, fi+2=90o, yi+2=0o
fi+1=60o, yi+1=30o, fi+2=60o, yi+2=30o
fi+1=-60o, yi+1=120o, fi+2=80o, yi+1=0o
fi+1=60o, yi+1=-120o, fi+2=-80o, yi+1=0o
fi+1=-80o, yi+1=80o, fi+2=80o, yi+2=-80o
cis-proline
|yi+1|80o, |fi+2|<60o
|yi+1|60o, |fi+2|180o
Helical structures
a-helical structure predicted
by L. Pauling; the name was
given after classification of
X-ray diagrams.
Helices do have
handedness.
Geometrical parameters of helices
Average parameters of helical structures
Type
H-bond
Turns
closed
by Hbond
radius
Idealized hydrogen-bonded helical structures:
310-helix (left), a-helix (middle), p-helix (right)
a-helices: deformations
bifurcated or mismatched H-bonds disrupt periodic structure
Bifurcated hydrogen
bonds (1,4 and 1,5) at
helix ends.
1,3-, and 1,4-hydrogen 1,6-hydrogen bonds at
helix ends.
bonds at helix ends.
Zniekształcenia a-helis
dodatkowe wiązania wodorowe na końcach
helis (wiązanie wodorowe rozwidlone
lub zmiana wiązania 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
Helix deformation (kink)
Example from myoglobin structure. The kink angle is up to 20o
Additional H-bonds with water molecules
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
Helix breaking by Pro residues
Ring constraint
No amide hydrogen
O
C-O
N
H
Helix capping
The first and
Izolowana
12-resztowa
the last residue
a-helisa
are the
posiada
capping
12 grup
residues
donorowych NH oraz 12 grup
akceptorowych CO wiązania wodorowego (w obrębie łańcucha głównego). W 12
The N1 and C1 residues possess f and y angle values typical of an a-helix
resztowej helisie może utworzyć się tylko 8 wewnątrzcząsteczkowych wiązań
wodorowych.
About
48% residues
N- i C-Końcowy
in Ncap-N1-N2-N3
fragmentfragments
helisy zawiera
and about
więc35%
4 wolne
of residues
donory in
NH
-C3-C2i4
wolnecapC1-C
akceptory
fragments
COforms
wiązań
hydrogen
wodorowych.
bonds in
Kompensacją
which side-chain
tej niedogodności
groups take part.
jest
występowanie polarnych reszt aa na N- i C-końcu helisy. N- i C-Końcowe fragmenty
helis wykazują dodatkowo różne preferencje co do określonych reszt aa.
...-N’’-N’-Ncap-N1-N2-N3-...........................-C3-C2-C1-Ccap-C’-C’’-...
Residue preferences to occur at end or
close-to-end positions
a-helices always have a large dipole moment
Side chain arrangement in helices
Contact interactions occur
between the side chains
separated by 3 residues in
amino-acid sequence
Schematic representation a-helices: helical wheel
3.6 residues per turn = a residue every 100o.
Examples of helical
wheels
Amphipatic (or amphiphilic) helices
One side contains hydrophobic aminoacids, 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
download cytochrome B562
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)
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.
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 (Y=120o), 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)
f and y angles of regular and polyproline helices
Structure
F
Y
w
a-helix
-57
-47
180
+3.6
1.5
310-helix
-49
-26
180
+3.0
2.0
p-helix
-57
-70
180
+4.4
1.15
Polyproline I
-83
+158 0
+3.33
1.9
Polyproline II
-78
+149 180
-3.0
3.12
Polyproline III
-80
+150 180
+3.0
3.1
residues/turn
turns/residue
Deca-glycine in PPII and PPI without hydrogen atoms,
spacefill modells, CPK colouring
PPI-PRO.PDB
PPII-PRO.PDB
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).
The b-helix