Notes on Protein Structure - Primary, Secondary, Tertiary and Quaternary

Proteins are an important class of molecules found in all living cells. A protein is composed of one or more long chains of amino acids, the sequence of which corresponds to the DNA sequence of the gene that encodes it. Proteins play a variety of roles (functions) in the cell, including structural (cytoskeleton), mechanical (muscle), biochemical (enzymes), and cell signalling (hormones). Proteins are also an essential part of diet.

There are 4 levels of structure in proteins

  
       Primary, Secondary, Tertiary, Quaternary

Primary Structure

The linear sequence of amino acids joined together by peptide bonds is termed the primary structure of the protein

Val-Glu-Leu-Ala-Gly-Lys-Met

Peptide bond

• A protein is a linear sequence of amino acids linked together by peptide bonds
• Peptide bonds have a partial double-bond character (rigid & planar)
• Generally in the trans configuration

Secondary Structure

Refers to the regular folding of regions of the polypeptide chain

Most common type of Secondary Structure: 

(A) α-helix (a spiral) 

(B) β-pleated sheet (folds)

Secondary Structural elements are stabilized by extensive hydrogen bonding

(A) α-helix 

• α-helix is a cylindrical, rod-like helical arrangement of the amino acids in the polypeptide chain which is maintained by hydrogen bonds parallel to the helix axis.In a α-helix there are 3.6 amino acids per turn of the helix covering a distance of 0.54 nm. 

  (B) β-pleated sheet

• Hydrogen bonds form between adjacent sections of polypeptides that are either running in the same direction (parallel β-pleated sheet) or in the opposite direction (anti parallel β-pleated sheet).
• Motifs (Super secondary structures) are produced by packing side chains from adjacent secondary elements close to each other.

    Tertiary Structure

• Refers to the 3-dimesional (spatial) arrangement of all amino acids in the polypeptide chain.
• Biologically active (native) conformation stabilized by disulphide bonds, ionic bonds, hydrogen bonds and hydrophobic interactions.
• Domains are the functional and the three dimensional structural unit of a polypeptide. They are formed from combination of motifs

   Quaternary Structure

·     Proteins consists of more than one polypeptide chain have quaternary structure. The poly peptides are held together by covalent (disulphide bonds) or non covalent interactions (hydrophobic interactions, electrostatic forces, hydrogen bonding).

·        e.g. Hemoglobin made up of 4 polypeptide chains, two α-chains and two β-chains(α₂β₂), each with a heme prosthetic group.

Protein Structure Determination

•     X-Ray crystallography
•     Myoglobin is the first protein to have its 3 dimensional structure solved.
•     Nuclear Magnetic Resonance (NMR) Spectroscopy

Protein Denaturation & Misfolding

Nobel Prize in this area

•      Frederick Sanger (1958) Chemistry-Primary structure of proteins
•     John C.Kendrew & Max F.Perutz (1962) Chemistry-Three dimensional structure of globular proteins
•    Christian B.Anfinsen (1972) Chemistry- Relationship between primary and tertiary structure of proteins
•     D.Carleton Gajdusek (1976) Medicine & Physiology- Prions based diseases
   Stanley B. Prusiner (1997) Medicine & Physiology-Protein nature of Prions