PROTEIN STRUCTURE
Protein structure can be considered at four levels:
1) Primary structure
2) Secondary structure
3) Tertiary structure
4) Quaternary structure
Note: - All proteins have their own specific primary structure, amino acids sequence, determined
by their genes - Different proteins have different extent of secondary structure. Some have none.
- All intracellular globular proteins have a tertiary structure. - Proteins made of more than one
subunit [polypeptide] have quaternary structure.
1) Primary structure
It is the sequence of amino acids in a protein. - Different proteins differ from each other in their
primary structure but every protein has a free carboxyl end terminal and a free amino end
terminal.
- The bonds responsible for the primary structure are: the covalent bonds:
The peptide bonds (C – N) The disulfide bonds (S – S).
The disulfide bonds (if present) between two cysteine residues of the same polypeptide chain or
between different polypeptide chains. The primary structure is therefore very stable due to these
bonds. - Peptide bonds are not broken by normal handling nor that conditions that denature
proteins such as heating. - Prolonged exposure to strong acid or base at elevated temperature is
required to hydrolyze these bonds (peptide bond), non-enzymatically. - Treatment with strong
reducing agents disrupts the disulfide bridges and effects the biological properties of the proteins.
2) Secondary structure
It is the spatial arrangement of amino acid residues that are near one another in the linear
sequence of the polypeptide chain. The secondary structure are of three types: a) The α-helix b)
β-pleated sheets c) Collagen helix.
The bonds responsible for stability of secondary structure: The secondary structure is stabilized
by a hydrogen bonds between peptide bond groups (i.e. between NH group of one amino acid
residue and the carbonyl oxygen (C=O) of other amino acid).
a) α-helix: - It is a spiral structure. - The polypeptide backbone is tightly wound around the long
axis of the molecule and the R-groups of amino acid residues protrude outward from the helical
backbone. - The repeating unit is a single turn of the helix, which extends about 5.4 ͦA along the
long axis. -Each helical turn includes 3.6 amino acid residues - In all proteins, the helical twist of
the α-helix is righthanded. The bonds responsible for stability of α-helix: It is stabilized by a
hydrogen bonds between peptide bond groups.
An α-helix permits the formation of intrachain hydrogen bonds between successive coils of the
helix, parallel to the long axis of the helix. -The hydrogen bond formed between the hydrogen
atom attached to the electronegative nitrogen atom of each peptide linkage and the
electronegative carbonyl oxygen atom of the fourth amino acid on the amino terminal side of it
in the helix. - Every polypeptide bond of the chain participates in such hydrogen bonding. - Each
successive turn of the α-helix is held to the adjacent turns by three to four hydrogen bonds,
conferring significant stability in the overall structure.
b) β-pleated sheet: - In the β-conformation, the backbone of the polypeptide chain is extended
into a zigzag rather than a helical structure. - The zigzag polypeptide chains can be arranged side
by side to form a structure resembling a series of pleats, such a structure is called a β-pleated
sheet. - The R-groups of adjacent amino acids protrude from the zigzag structure in opposite
directions, creating the alternating pattern. - Hydrogen bonds form between adjacent segments of
polypeptide chain β- pleated sheet are composed of two or more β-strands.
c) Collagen helix: Collagen is found in connective tissue such as tendons, cartilage, the organic
matrix of bone and the cornea of the eye. Collagen molecules (tropocollagen – basic unit) consist
of three polypeptide, called α-chains (each α-chain is twisted into a left handed helix of 3 residue
per turn) which wrap around each other in a triple helix (right handed triple helix) forming a
rope-like structure. - Collagen is built of recurring subunit structure, triple -stranded
tropocollagen (triple helix) molecules, having distinctive heads. These arranged head to tail in
many parallel bundles, but the heads are staggered. - Between the end of one triple helix and the
beginning of the next is a gap that may provide a site for deposition of hydroxyapatite crystals in
bone formation. - The polypeptide chains of tropocollagen are covalently cross linked by
dehydrolysinonorleucine residues formed by an enzymatic reaction between two lysine residues
of adjacent tropocollagen subunits. The three polypeptide chains are held together by hydrogen
bonds between chains.
3) Tertiary structure
Refer to the spatial arrangement of amino acid residues that are far apart in the linear sequence
(i.e in the primary structure), so the polypeptide chain is folded into three dimension. -Tertiary
structure is three-dimensional conformation of a polymer in its native folded state. - The unique
three-dimensional structure of each polypeptide is determined by its amino acids sequence. -
Interaction of the amino acid side chains guide the folding of the polypeptide chain to form a
compact structure.
Hydrophobic side chains are burried in the interior whereas hydrophilic groups are generally
found on the surface of the molecule. Bonds that stabilize tertiary structure: Non-covalent bonds
between R-groups (i.e between groups in the side chains). [weak bonds] a) Hydrophobic
interaction b) Hydrogen bonds c) Ionic interaction d) Disulphide bonds.
a) Hydrophobic interactions: it is the association between non-polar groups (hydrophobic
groups) in the side chains of amino acids.
b) Hydrogen bonds: A hydrogen bond is a type of attractive interaction between an
electronegative atom (such as oxygen or nitrogen) and a hydrogen atom bonded
covalently to another electronegative atom.
c) Ionic interaction (electrostatic interaction): Interaction between opposite charged groups
of the side chains of amino acids.
Example of 3ry structure: The structure of Myoglobin
-It is small globular protein (hemoprotein), present in heart and skeletal muscle. - It functions
both as a reservoir for oxygen and as an oxygen carrier that increases the rate of transport of
oxygen within the muscle cell. - Myoglobin consists of a single polypeptide chain of 153 amino
acid residues of known sequence and a single heme group.
4) Quaternary structure
Myoglobin structure is stabilized by Non-covalent bonds. - Proteins that are composed of more
than one polypeptide chain (subunits) show a fourth level of protein structure which is the
quaternary structure. Quaternary structure is the three-dimensional structure of a multisubunit
protein, particularly the manner in which the subunits fit together. Subunits may either function
independently of each other or may work cooperatively, as in hemoglobin. Quaternary structure -
The interaction between subunits are stabilized by the same forces that stabilize tertiary structure
(non-covalent bonds). Bonds that stabilize quaternary structure: a) Hydrophobic interaction b)
Hydrogen bonds c) Ionic interaction- Non-covalent bonds between R-groups (i.e between groups
in the side chains).
Example of 4ry structure: The structure of Hemoglobin
Hemoglobin is simple oligomeric protein. -It is found in red blood cells (RBC), where its main
function is to transport oxygen from the lungs to the capillaries of the tissues. - Hemoglobin is
hemoprotein, composed of four polypeptide chains and four heme groups. - The protein portion
(globin), consist of four polypeptide chains (two α-chains and two β-chains; α2β2 ) held together
by noncovalent interactions. -The α and β chains contain several segments of α-helix separated
by bends, with a tertiary structure very similar to that of the single polypeptide of myoglobin.