CHMI 2227E Biochemistry I

1. CHMI 2227EBiochemistry I Proteins: Secondary Structure Alpha Helix CHMI 2227 - E.R. Gauthier, Ph.D.

2. 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.

3. 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.

4. 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.

5. 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 CHMI 2227 - E.R. Gauthier, Ph.D. http://www.ccrc.uga.edu/~dmohnen/bcmb3100/lecturenoteschap4-06-4slides.pdf

6. 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 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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/lecturenoteschap4-06-4slides.pdf CHMI 2227 - E.R. Gauthier, Ph.D.

12. 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.

13. 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.

14. 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/protein/secondary_structure/alpha_helix/down/wheel.gif CHMI 2227 - E.R. Gauthier, Ph.D.

15. 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.

16. Two amphipathic α-helices 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 Coiled Coil Structure Molecular Biology of the Cell, 4th Edition CHMI 2227 - E.R. Gauthier, Ph.D.

17. 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.

18. 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.