1) A protein's structure is determined by its amino acid sequence and consists of four levels: primary, secondary, tertiary, and quaternary. 2) The two most common secondary structures are alpha helices and beta sheets, which are stabilized by hydrogen bonds between amino acids. 3) Tertiary structure describes the overall 3D shape of a protein formed by interactions between regions of the polypeptide chain distant in primary sequence. Quaternary structure involves interactions between multiple protein subunits.

1. Structural organization of
proteins

2. Protein
Peptide Bond

4. Few things should be remembered:
•Three dimensional structure of a protein is determined by its amino acid sequence.
•The function of a protein depends on its structure.
•An isolated protein usually exists in one or a small number of stable structural forms.
•The most important forces stabilizing the specific structures maintained by a given
protein are noncovalent interactions.

6. Primary Structure of Protein
• The primary structure of a protein is its linear
sequence of amino acids and the location of any
disulfide (-S-S-) bridges.

7. Basic structural units of proteins:
Secondary structure
α-helix β-sheet
Secondary structures, α-helix and β-
sheet, have regular hydrogen-bonding
patterns.

8. Three-dimensional structure of proteins
Tertiary structure
Quaternary structure

9. Hierarchical nature of protein structure
Primary structure (Amino acid sequence)
↓
Secondary structure （α-helix, β-sheet）
↓
Tertiary structure （Three-dimensional structure
formed by assembly of secondary structures）
↓
Quaternary structure （Structure formed by more than
one polypeptide chains）

10. Protein’s Secondary structure
Most proteins contain one or more stretches of
amino acids that take on a characteristic
structure in 3-D space. The most common of
these are the alpha helix and the beta
conformation.

11. Secondary structure
In 1951 Linus pauling and Robert Corey first proposed two types
of secondary structure:
1.Alpha Helix
2.Beta sheet
 Both of these secondary structures are held together by hydrogen bond
between CO and NH groups of peptide bonds
 An Alpha helix is formed when a region of a polypeptide chain coils
around itself , and H bond formed between CO and NH groups of peptide
bond separated by four amino acid residues .
 In a Beta sheet , Hydrogen bonds connect two parts of a polypeptide lying
side by side .

12. • Rigid peptide bonds, but other single bonds are free to rotate.
• The polypeptide backbone is tightly wound around an imaginary axis drawn
longitudinally through the middle of the helix.
• The R groups of the amino acids all protrude outward from the helical backbone.
• Repeating unit is a single turn of the helix which extends about 5.4ͦ along the long
axis.
• The helix makes a complete turn every 3.6 amino acids.
• The helical twist of α helix found in all proteins is right handed.
Alpha Helix

13. Why does the alpha helix form more readily than many other possible
conformations?
• Alpha helix makes optimal use of internal hydrogen bonds. The structure is
stabilized by a hydrogen bond between the hydrogen atom attached to the
electronegative nitrogen atom of a peptide linkage and the electronegative
carbonyl oxygen atom of the fourth amino acid on the amino terminal side of
that peptide bond.
Alpha Helix

15. Amino acid sequence affects Alpha Helix stability
Five different kinds of constraints affect the stability of an Alpha Helix:
1. The electrostatic repulsion (attraction) between successive amino acid
residues with charged R groups.
2. The bulkiness of adjucent R groups
3. The interactions between amino acid side chains spaced three ( or four)
residue apart.
4. The occurrence of Pro and Gly residues. Proline’s nitrogen is in the ring,
so it is not available to make hydrogen bond; glycine has more
conformational flexibility so it tends up to take coil structure.
5. The interaction between aa residues at the ends of the helical segment and
the electric dipole inherent to the Alpha helix, (e.c. a positively charged
amino acid at the amino terminal end is destabilizing)

17. Beta sheet
 In β-conformation, the backbone of the polypeptide chain is
extended into a zigzag rather than helical structure.
 The zigzag polypeptide chains can be arranged side by side to
form a structure resembling a series of pleats.
 The adjacent polypeptide chains in a β-sheet can be either
parallel or anti parallel.
 The repeat period is for parallel conformation=6.5 Angstrom
 The repeat period for antiparallel conformation= 7 Angstrom
 Example: Silk fibroin and fibroin of spider webs ( contains
Gly and Ala)

21. Beta Turns
 A turn is an element of secondary structure in proteins.
 Beta turns are connecting elements that links successive runs
of Alpha Helix and Beta conformation.
 Common beta turn connects the ends of two adjacent
segment of an antiparallel beta sheet. It involves 4 amino acid
residues, with the carbonyl oxygen of the first residue forms
hydrogen bonds with the amino group hydrogen of the fourth.
 Can be type 1 and 2.

23. Tertiary structure
• The overall 3 dimensional arrangement of all atoms in a
protein.
• Secondary structure refers to the spatial arrangement of
amino acids that are adjacent in the primary structure,
tertiary structure includes longer range aspects of amino acid
sequence, aa that are far apart in the polypeptide sequence
and that reside in different type of secondary structure may
interact within the completely folded structure of a protein.
• Tertiary structure is the folding of the polypeptide chain as a
result of interactions between the side chains of amino acids
that lie in regions of primary sequence.
• E.g. Ribonuclease.

24. Quaternary structure
• Some proteins contain two or more separate
polypeptide chains or subunits, which may be
identical or different. The arrangement of
these protein subunits in three dimensional
complexes constitute quaternary structure
E.g. Hemoglobin.