secondary structure of proteins : turns and helices

SECONDARY STRUCTURE OF PROTEINS: TURNS AND

HELICES

Levels of protein structure organization

60% 40%

Hybrid of two canonical structures

Peptide bond geometry

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 angles

1=0

1 2 3

Dihedrals with which to describe polypeptide geometry

main chain

side chain

Skan z wykresem energii

Peptide group: cis-trans isomerization

Because of peptide group planarity, main chain conformation is effectively defined by the and angles.

Side chain conformations

The dihedral angles with which to describe the geometry of disulfide bridges

Some and pairs are not allowed due to steric overlap (e.g, ==0o)

The Ramachandran map

Conformations of a terminally-blocked amino-acid residue

C7eq

C7ax

E Zimmerman, Pottle, Nemethy, Scheraga, Macromolecules, 10, 1-9 (1977)

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

L-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)

- and -turns

-turn (i+1=-79o, i+1=69o) -turns

Types of -turns in proteins

Hutchinson and Thornton, Protein Sci., 3, 2207-2216 (1994)

Older classification

Lewis, Momany, Scheraga, Biochim. Biophys. Acta, 303, 211-229 (1973)

i+1=-60o, i+1=-30o, i+2=-90o, i+2=0o i+1=60o, i+1=30o, i+2=90o, i+2=0o

i+1=-60o, i+1=-30o, i+2=-60o, i+2=-30o i+1=60o, i+1=30o, i+2=60o, i+2=30o

i+1=-60o, i+1=120o, i+2=80o, i+1=0o i+1=60o, i+1=-120o, i+2=-80o, i+1=0o

i+1=-80o, i+1=80o, i+2=80o, i+2=-80o

i+1|80o, |i+2|<60o

i+1|60o, |i+2|180o

cis-proline

Helical structures

-helical structure predicted by L. Pauling; the name was given after classification of X-ray diagrams.

Helices do have handedness.

Average parameters of helical structures

TypeH-bond Turns

closed by H-bond

radius

Geometrical parameters of helices

Idealized hydrogen-bonded helical structures: 310-helix (left), -helix (middle), -helix (right)

-helices: deformationsbifurcated or mismatched H-bonds disrupt periodic structure

Bifurcated hydrogen bonds (1,4 and 1,5) at helix ends.

1,3-, and 1,4-hydrogen bonds at helix ends.

1,6-hydrogen bonds at helix ends.

Zniekształcenia -helisdodatkowe wiązania wodorowe na końcachhelis (wiązanie wodorowe rozwidlonelub 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 -helix in phosphoglyceryl aldehyde dehydrogenase

N

H

C-O

ONo amide hydrogen

Helix breaking by Pro residues

Ring constraint

Helix capping

Izolowana 12-resztowa -helisa posiada 12 grup donorowych NH oraz 12 grup akceptorowych CO wiązania wodorowego (w obrębie łańcucha głównego). W 12 resztowej helisie może utworzyć się tylko 8 wewnątrzcząsteczkowych wiązań wodorowych. N- i C-Końcowy fragment helisy zawiera więc 4 wolne donory NH i 4 wolne akceptory CO wiązań wodorowych. Kompensacją tej niedogodności 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’’-...

The first and the last residue are the capping residues

The N1 and C1 residues possess and angle values typical of an a-helix

About 48% residues in Ncap-N1-N2-N3 fragments and about 35% of residues in -C3-C2-C1-Ccap- fragments forms hydrogen bonds in which side-chain groups take part.

Residue preferences to occur at end or close-to-end positions

-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 -helices: helical wheel

3.6 residues per turn = a residue every 100o.

Examples of helical wheels

Amphipatic (or amphiphilic) helices

Hydrophobic

Hydrophilic

hydrophilic head groupaliphatic carbon chain lipid

bilayer

Amphipatic helices often interact with lipid membranes

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

download cytochrome B562

Length of -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.

C2 (half-chair) conformations of C-endo L-proline

CS (envelope) conformation of C-endo L-proline peptide group at the trans position with respect to C-H (=120o), as in collagene

CS (envelope) of C-egzo L-proline with the peptide group at the cis’ orientation with respect to C-H (=-60o)

Polyproline ring conformations

Structure residues/turn turns/residue

-helix -57 -47 180 +3.6 1.5

310-helix -49 -26 180 +3.0 2.0

-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

and angles of regular and polyproline helices

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).

Deca-glycine in PPII and PPI without hydrogen atoms, spacefill modells, CPK colouring

PPI-PRO.PDB

PPII-PRO.PDB

The -helix