Biochemistry 302 Lecture Outline: Protein Secondary, Tertiary, Quaternary Structure

I. Factors Influencing Secondary Structure Formation

A. heirarchy of protein structure (figure 1)

B. amide bond planarity (figure 2)

1) steric hindrance (model)

2) Y (psi) C2- a , F (phi) N1-a

C. hydrogen bonding etc. (figure 3)

II. a -helix - Pauling and Corey, models and van der Waals radii

A. basic structure (figure 4, 5)

1) right handed helix

2) R-groups radiate away from axis

3) 1.5 Å/residue, 100° rotation/residue, 5 Å across(C1 to C1)

4) 3.6 residues/helix turn

5) 5.4 Å/helix turn

6) stability

- H-bond between carboxyl oxygen of n and amide proton of n+4

- close packing (side-by-side van der Waals radii) in center of helix, note the center is not hollow

III. b -sheets - Pauling and Corey again

A. anti-parallel b -pleated sheet - most common sheet (figure 6)

1) amide proton from amino acid on one sheet forms H-bond with caboxyl oxygen of amino acid of other sheet which run in opposite direction

2) 7.0 Å/amino acid run

3) several sheets can exist side by side (figure 6)

4) silk example (figure 7)

- anti-parallel sheet

- alternating glycine and alanine/serine

- interlocking side chains give differently spaced layers of sheets which gives strength

B. parallel b -pleated sheet least common sheet (figure 6)

1) amide proton from amino acid on one sheet forms H-bond with caboxyl oxygen of amino acid of other sheet which run in same direction

2) 6.5 Å/amino acid run

IV. Comparisons/Examples

A. a -helix and b -sheet (figure 8)

- notice zig-zag structure of sheet, its not really flat although depicted that way often

- Ramachandran Plot (figure 9)

B. fibrous proteins (structures determined from them)

1) a -keritin (hair), from which comes a -helix (figure 10)

2) b -sheets

- silk, already shown

- b -keritins, from which comes b -sheets

3) collagen (figure 11)

- G, P, hydroxyP alternating

- P repeats rule out a -helix and b -sheet

- 3 left handed helical peptides

- G towards center of triple helix

- interchain H-bonds account for strength

C. globular proteins (figure 12)

1) contain combination of a -helix and b -sheet as well as other structures and folding motifs

2) inclusive of nearly all enzymes and regulatory proteins

3) very structurally diverse

4) example of how secondary structure is important for biological function: helix-turn-helix (figure 13, 14)

V. Thermodynamics of Protein Folding

DG = DH - TDS

DG more negative to be spontaneous

DH more negative (make bonds/interactions)

DS more positive (create more disorder)

How is this possible? (see parenthesis)

VI. Tertiary Structure Folding

A. b-bends (figure 15)

B. various connectivities (figure 16)

C. sheet connectivity (figure 17, belt example)

D. sheet crossover (figure 18)

E. twisted sheet, or saddle (figure 19)

F. beta barrel (figure 19)

G. examples

1) saddle and beta barrel (figure 20)

2) four helical bundle (figure 21)

3) "faced" proteins (figure 22, 23)

VII. Quaternary structures

A. Why? for cooperativity and enhanced regulation

B. examples

1) hemoglobin (figure 24)

2) muscle (figure 25, 26)

3) the immune system (figure 27, 28)

4) flagella (figure 29)

5) cooperative function in aspartate transcarbamoylase (figure 30)

6) membrane bound protein receptor/signal systems (figure 31)

7) ribosome (figure 32)

8) polymerization of enzyme capsules (figure 33, 34)