CHMI 2227E
Biochemistry I
Proteins:
-Secondary
-Alpha
Structure
Helix
CHMI 2227 - E.R. Gauthier, Ph.D.
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Secondary Structure

It is the ordered arrangement or conformation of
amino acids in localized regions of a polypeptide
or protein molecule;

Hydrogen bonding plays an important role in
stabilizing these folding patterns;

Polypeptide chains can fold into regular
structures such as the alpha helix, the beta
sheet and turns and loops
CHMI 2227 - E.R. Gauthier, Ph.D.
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Alpha Helix

The α-helix was proposed in 1950 by Linus
Pauling and Robert Corey;

They considered the dimensions of peptide
groups, possible steric constraints and
opportunities for stabilization by formation of
hydrogen bonds;

Their model accounted for the major repeat
observed in the structure of the fibrous protein
called α-keratin
CHMI 2227 - E.R. Gauthier, Ph.D.
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Left and Right Handed Helices

An α-helix can be
either a right- or a lefthanded screw;

The α-helices found
in proteins are almost
always right-handed
http://www.fiu.edu/~bch3033/Handouts/Lh4Ch04Prot.pdf
CHMI 2227 - E.R. Gauthier, Ph.D.
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Alpha Helix Structure

The pitch of
the helix is
0.54nm, the
rise is 0.15nm
and the
number of
amino acid
residues for
one
complete
turn is 3.6
http://www.ccrc.uga.edu/~dmohnen/bcmb3100/lecturenoteschap4-06-4slides.pdf
CHMI 2227 - E.R. Gauthier, Ph.D.
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Importance of polar peptide bond in
forming intrachain H-bonds in α-helix

Note: Peptide bond is
polar!

The carbonyl oxygen has
a partial negative charge
and can serve as a
hydrogen acceptor in Hbonds;

The nitrogen has a partial
positive charge and the
NH group can serve as a
hydrogen donor in Hbonds
CHMI 2227 - E.R. Gauthier, Ph.D.
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Alpha Helix Hydrogen Bonds

Within an α-helix, each carbonyl oxygen (residue n) of
the polypeptide backbone is hydrogen-bonded to the
backbone amide hydrogen of the fourth residue further
toward the C-terminus (residue n + 4);

These H-bonds tend to “lock in” rotation around the N-Cα
and the Cα-C bonds restricting the Φ and Ψ angles to a
narrow range
CHMI 2227 - E.R. Gauthier, Ph.D.
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Alpha Helix Hydrogen Bonds

Side views of
the alpha
helix that
shows the
hydrogen
bonds
(dashed
lines)
between NH
and CO
groups
Molecular Biology of the Cell, 4th
Edition
CHMI 2227 - E.R. Gauthier, Ph.D.
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Alpha Helix Psi and Phi Angles

The Φ and Ψ angles of
each residue in an α-helix
are similar. They cluster
in the Ramachandran plot
at a Φ value of -57° and a
Ψ value of -47°.

The similarity of these
values is what gives the
α-helix a regular,
repeating structure
CHMI 2227 - E.R. Gauthier, Ph.D.
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Alpha Helix Intrahelical H-bonds

H-bonds between amino acid residues are
especially stable in the hydrophobic interior of
a protein where water molecules do not enter
and therefore cannot compete for H-bonding

In an α-helix, all the carbonyl groups point
toward the C-terminus. Since each peptide
group is polar and all the H-bonds point in the
same direction, the entire helix is a dipole with a
positive N-terminus and a negative C-terminus
CHMI 2227 - E.R. Gauthier, Ph.D.
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Alpha Helix Conformation

The side chains of the amino acids in an α-helix
point outward from the cylinder of the helix
http://www.ccrc.uga.edu/~dmohnen/bcmb3100/lecturenotesch
ap4-06-4slides.pdf
CHMI 2227 - E.R. Gauthier, Ph.D.
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Stability of the Alpha Helix

The stability of the α-helix is affected by the identity of the
side chains:

Electrostatic repulsion between amino acids having same charged
R groups separated by 4 residues (destabilizes)

Steric hindrance between adjacent R groups (destabilizes)


i.e. aromatic amino acids
Interactions (electrostatic or hydrophobic) between R groups
situated 3 to 4 amino acid residues away (stabilizes)

i.e. positively charged amino acid situated 3 to 4 amino acids away from
a negatively charged amino acid

Presence of proline residue destabilizes the α-helice because the
rotation N-Cα is impossible

Presence of glycine
CHMI 2227 - E.R. Gauthier, Ph.D.
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Amino Acid Residues in Alpha Helix

Some amino acids are found in α-helical conformation due
to stability:

Ala: small, uncharged R group and fits well into the α-helical
conformation;

Tyr/Asn: bulky R groups so they are less common

Gly: R group is a single H atom and destabilizes the structure since
rotation around the Cα is unconstrained


For this reason, many α-helices begin or end with Gly
Pro: least common residue in α-helix because of its rigid cyclic side
chain disrupts the helical structure by occupying space that a
neighboring residue of the helix would otherwise occupy
CHMI 2227 - E.R. Gauthier, Ph.D.
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Alpha Helix can be Amphipathic

Many α-helices have
hydrophilic amino acids on
one face of the helix cylinder
and hydrophobic amino
acids on the opposite face
(amphipathic nature);

This is easier to see when
the amino acid sequence is
drawn as a spiral, called a
helical wheel representing
the helix viewed along its
axis
http://web.chemistry.gatech.edu/~williams/bCourse_Information/6521/p
rotein/secondary_structure/alpha_helix/down/wheel.gif
CHMI 2227 - E.R. Gauthier, Ph.D.
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Amphipathic helices on surfaces of
proteins

Amphipathic helices are
often located on the
surface of a protein, with
the hydrophilic side chains
facing outward (toward the
aqueous solvent) and the
hydrophobic side chains
facing inward (toward the
hydrophobic interior);

In this image, the
hydrophobic residues are in
blue (inward) and
hydrophilic residues are in
red (outward);
CHMI 2227 - E.R. Gauthier, Ph.D.
http://www.ccrc.uga.edu/~dmohnen/bcmb3100/lecturenoteschap4-064slides.pdf
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Coiled Coil Structure

Two amphipathic αhelices can interact to
produce an extended
coiled coil structure
where two helices
wrap around each
other with their
hydrophobic faces in
contact and their
hydrophilic faces
exposed to the
solvent
Molecular Biology of the Cell, 4th Edition
CHMI 2227 - E.R. Gauthier, Ph.D.
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Coiled Coil Structure: Example

A common structure in DNAbinding proteins is called a
leucine zipper;

Two helices are “zippered”
together by the hydrophobic
interactions
http://www.ccrc.uga.edu/~dmohnen/bcmb3100/lecturenoteschap4-064slides.pdf
CHMI 2227 - E.R. Gauthier, Ph.D.
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Coiled Coil Structure: Alpha keratin

α-keratin is found in hair and nails;

Two molecules of α-keratin will form a coiled coil structure whereas
the two helices are maintained by disulfide bonds

The coiled coil will pair up with other coiled coils forming
protofilaments and protofibrils;

Four protofibrils will form a keratin intermediate filament
http://www.fiu.edu/~bch3033/Handouts/Lh4Ch04Prot.pdf
CHMI 2227 - E.R. Gauthier, Ph.D.
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