Secondary Structure of Polypeptides

Secondary Structure of Polypeptides

Solving Secondary Structures

  • In the late 1940s to early 1950s, two groups aimed to determine the secondary structure of polypeptides.
  • This involved identifying short-range, regular, repeating structures formed when a polypeptide transitions from its primary to secondary structure.
Approaches to Solving Secondary Structure

  1. Paper and Pencil Method:

    • One group, led by a researcher with a difficult-to-pronounce name (but whose last name is pronounceable), used a manual approach.
    • They drew polypeptides on paper and considered rotations around the carbon-carbon bonds involving the alpha carbon of amino acids.
    • They calculated whether each structure was "allowed" based on the absence of electron cloud overlap or steric hindrance (atoms getting in the way of each other).
    • This was done with limited computing power, as computers in the 1940s were large and less powerful than modern devices.

  2. Experimental Method:

    • Linus Pauling and Robert Corey took a more experimental route.
    • They isolated and synthesized peptides, crystallized them, and used X-ray crystallography.
    • X-ray crystallography allows the localization of individual atoms within the crystal, enabling the determination of secondary structure.
Nobel Prize
  • Both groups were awarded the Nobel Prize in the early 1950s for their work on solving the secondary structure of proteins.
  • It was Linus Pauling's second Nobel Prize; his first was in chemistry for his work on electronegativity.
  • This second prize was in medicine, as biochemistry is often categorized under medicine.

Allowed Structures

  • The groups identified six allowed structures.
  • The fact that both groups, using different approaches, arrived at the same six structures was a validation of their findings.

  1. Circular Structure:

    • A structure where the amino terminus reacts with the carboxy terminus.
    • Instead of a linear peptide, a circular molecule is formed.

  2. Left-Handed Helix:

    • A helical structure that coils in a left-handed direction.

  3. Right-Handed Helix:

    • A helical structure that coils in a right-handed direction.

  4. Sheet-Like Structures:

    • Structures where polypeptide chains stack on top of each other, forming a drapery-like arrangement.

  5. Triple Helical Structure:

    • Allowed if the primary structure is rich in glycine.
    • The small hydrogen side chain of glycine allows three strands of polypeptide chain to coil around each other.
    • Few proteins exhibit this structure.
    • Example: Collagen

  6. Turns or Bends:

    • Structures where the polypeptide chain changes direction by approximately 180 degrees.

Observations and Enantiomers

  • Circular structures have not been observed in nature, although they are theoretically possible.
  • The reasons for this avoidance of circular structures in nature are unclear.
  • The original calculations used both d and l enantiomers but Linus Pauling used naturally occurring peptides with only the l enantiomer.
  • L enantiomers of amino acids cannot form left-handed helices.
  • D enantiomers can form left-handed helices but cannot form