lecture 5 part 1

Alpha Helices

• Structure and Orientation

  • Right-handed helix: if the thumb points toward the C-terminus, fingers curl in the direction of the helix.

  • Irregularity in the helix: 3.6 amino acids per turn, causing amino acid side chains (R groups) to project outwards and not align uniformly.

• R Groups Positioning

  • R groups in alpha helices are projecting out into space, whereas the interior does not contain R groups.

  • The structure contributes to the role of proteins being functional and active, as R groups are ready to interact with other molecules.

• Bond Interactions

  • Bond angles and steric hindrance drive the formation and stability of the alpha helix.

  • Hydrophobic Exclusion: Water tends to exclude hydrophobic carbon chains, pushing them into the interior of the helix, stabilizing it.

  • Backbone stabilizes with internal hydrogen bonds between carbonyls and nitrogens, making the structure stable despite the relatively weak hydrogen bonds (5-10 kJ/mol).

Stability and Interactions of Alpha Helices

• Comparison with Protein Function

  • Most proteins rely on helix structure as a robust building block, similar to how solid Legos are used to construct towers.

  • Alpha helices may not form if destabilized by unfavorable R group interactions, particularly those involving charges that repel each other.

• N to N+4 Rule for Interactions

  • The most stable interactions in helices occur between residues that are 3-4 positions apart in sequence (n and n+4 interactions).

  • Example: Analysis of interactions based on residue positions helps predict stability and folding potential of helices.

Beta Strands

• Structure of Beta Strands

  • If an alpha helix is destabilized, a peptide may prefer to adopt a beta strand formation (considered less stable than alpha helices).

  • The n to n+2 rule governs interactions in beta strands, with R groups projecting alternatively above and below the plane of the strand.

• Hydrogen Bonding in Beta Strands

  • Hydrogen bonds form between backbone amide groups in neighboring strands, stabilizing the structure.

  • Stability considerations include identifying favorable residual pairings and distances among R groups.

Protein Folding Dynamics

• Primary to Secondary Structures

  • Proteins start with a primary structure (sequence of amino acids). They preferentially fold into alpha helices unless destabilized.

  • If alpha helices cannot form, beta sheets may arise as the next secondary structure.

  • If neither structure is stable, the protein may adopt a 'random coil' conformation.

• Structure Contextualization

  • Secondary structures interact rapidly and spontaneously as they are synthesized at the ribosome—folding occurs almost immediately.

  • Structural transitions are influenced by environmental conditions and the particular R group arrangements.

Examples of Protein Structure and Functionality

• Keratin

  • Keratin forms coiled coils for strength and stability; prevalent in hair, nails, and skin.

  • Coiled coils are formed by helices wrapping around one another, maximizing attractive R group interactions.

• Silk

  • Silk produced by silkworms consists predominantly of beta sheets. It is known for its nonpolar property which repels water, making it smooth and slippery.

  • Silk's structure relies on its highly nonpolar R groups (e.g., alanine and glycine), forming strong hydrogen bonds in a crystalline-like arrangement.

Structural Considerations and Summary

• Hydrogen Bonding and Intermolecular Forces

  • R groups influence interactions within and between proteins, determining stability and functionality in tertiary and quaternary structures.

  • Cysteine's thiol group can form disulfide bonds, reinforcing protein structure through stronger covalent bonds (approx. 230 kJ/mol).

• Role of Environment

  • Humidity alters interactions within proteins, adding or removing water molecules that can influence hydrogen bonding and structural form.

  • Tertiary Structure: Interactions among the R groups define a protein's active form, leading to potential biological functions (e.g., enzymatic activity).

• Protein Folding Speed

  • Average folding time for proteins in E. coli can occur around half a second, demonstrating how rapidly proteins can achieve their functional states enduringly.