CHMI 2227E Biochemistry I

Proteins:

Secondary Structure Alpha 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

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CHMI 2227 - E.R. Gauthier, Ph.D.

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 left handed 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:

polar

!

Peptide bond is  The carbonyl oxygen has a partial

negative

hydrogen charge and can serve as a

acceptor

in H bonds;  The nitrogen has a partial

positive

charge and the NH group can serve as a hydrogen

donor

in H bonds 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 C α-C bonds restricting the Φ and Ψ angles to a narrow range

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CHMI 2227 - E.R. Gauthier, Ph.D.

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, 4 th 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

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CHMI 2227 - E.R. Gauthier, Ph.D.

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

rotation N-C α is impossible the α-helice because the  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 C α 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

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CHMI 2227 - E.R. Gauthier, Ph.D.

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); http://www.ccrc.uga.edu/~dmohnen/bcmb3100/lecturenoteschap4-06 4slides.pdf

CHMI 2227 - E.R. Gauthier, Ph.D.

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Coiled Coil Structure

 Two amphipathic other with their α helices can interact to produce an extended

coiled coil structure

where two helices wrap around each hydrophobic faces in contact and their hydrophilic faces exposed to the solvent Molecular Biology of the Cell, 4 th Edition CHMI 2227 - E.R. Gauthier, Ph.D.

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Coiled Coil Structure: Example

 A common structure in DNA binding proteins is called a leucine zipper;  Two helices are “zippered” together by the hydrophobic interactions http://www.ccrc.uga.edu/~dmohnen/bcmb3100/lecturenoteschap4-06 4slides.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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