Clinical Biochemistry Lecture 3: Protein Structure

Primary Structure of Proteins

• The sequence of amino acids forming the backbone of proteins are joined covalently by peptide bonds.
• Peptide bonds are formed between the α-carboxyl group of one amino acid and the α-amino group of another with the elimination of a water molecule.
• Clinical importance: many genetic diseases are due to abnormal amino acid sequences, and knowledge of primary structure can be used to diagnose or study the disease (e.g., Sickle cell disease).
• Proinsulin is a single polypeptide chain with 86 amino acid, converted to active insulin by loss of C-peptide.

Secondary Structure of Proteins

• Hydrogen bonding between the hydrogen of NH and oxygen of C=O groups of the polypeptide chain occurs, forming secondary structure.
• Two important kinds of secondary structure:
  • α-Helix (helicoidal structure): stabilized by hydrogen bonds between NH and CO groups of the same chain, with an optimal nitrogen to oxygen (N-O) distance of 2.8 Å.
  • β-Pleated sheet structure: composed of two or more polypeptide chains, stabilized by hydrogen bonds between NH and C=O groups in different polypeptide chains.

Tertiary Structure

• The peptide chain, with its secondary structure, may be further folded and twisted about itself, forming a three-dimensional arrangement of the polypeptide chain.
• Amino acid residues distant from each other in the sequence can be brought near due to folding, forming regions essential for protein function (e.g., active site or catalytic site of enzymes).
• Tertiary structure is stabilized by:
  • Hydrogen bonds
  • Hydrophobic interactions
  • Van der Waals forces
  • Disulfide bond
  • Ionic (electrostatic) bonds or salt bridges.

Quaternary Structure of Protein

• Only proteins with more than one polypeptide chain (polymeric) have a quaternary structure.
• Not all proteins are polymeric, some are monomeric (e.g., myoglobin).
• The arrangement of polymeric polypeptide subunits in three-dimensional complexes is called the quaternary structure of the protein.
• Examples of proteins with quaternary structure: Hemoglobin (Hb), Lactate dehydrogenase.
• The subunits of polymeric protein are held together or stabilized by:
  • Hydrophobic interactions
  • Hydrogen bond
  • Ionic bonds
  • Van der Waals forces.