Module 4: The Three-Dimensional Structure of Proteins

Flashcards covering the characteristics of peptide bonds, the four levels of protein structure, specific secondary structures (alpha-helix, beta-sheet), and examples of fibrous proteins like keratin, collagen, and silk, as well as prion diseases.

How do peptide bonds form and what molecule is generated as a byproduct?

Peptide bonds form by condensation reactions involving the generation of a water molecule.

Why are the six atoms of a peptide bond group considered rigid and planar?

Due to the partial double-bond characteristic of the $C-N$ peptide bond, which restricts rotation.

Which configuration of the peptide bond is more common and why?

The trans configuration is more common because the cis configuration is more likely to cause steric interference between side chain groups.

Define the four levels of protein structure.

Primary: linear sequence of amino acids; Secondary: localized patterns of folding; Tertiary: final folding pattern of a single polypeptide; Quaternary: folding pattern for multiple polypeptides.

In what direction is a primary protein structure sequence presented?

From the $N$ (amino) terminus to the $C$ (carboxyl) terminus.

What interactions maintain secondary structure in a polypeptide?

Hydrogen bonds between amide and carbonyl groups of the main-chain.

What are the two key rules for viable forms of secondary structure?

• Make lots of backbone hydrogen bonds.

• Avoid steric clashes (use allowed φ and ψ angles).

What are the names of the two bonds flanking the $\alpha$-carbon that have freedom of rotation?

Phi ($\Phi$) $C\alpha-N$ and Psi ($\psi$) $C\alpha-C$.

What tool is used to visualize all possible combinations of phi and psi angles?

Ramachandran plots.

Describe the basic structural parameters of an $\alpha$-Helix.

It is a right-handed helix with $3.6$ residues per turn.

What is the specific hydrogen bonding pattern in an $\alpha$-Helix?

The carbonyl group of residue $n$ hydrogen bonds with the amide group of residue $n+4$.

Why are Proline and Glycine uncommon in $\alpha$-helicies?

Proline is avoided due to its rigidity, and Glycine is avoided due to its extreme flexibility.

Describe the dipole of an $\alpha$-helix.

The $N$ terminus has a partial positive dipole charge and the $C$ terminus has a partial negative dipole charge.

What creates an amphipathic $\alpha$-helix?

The positioning of hydrophobic and hydrophilic residues within the primary structure so that the helix has polar and non-polar faces.

Why are anti-parallel $\beta$ sheets more stable than parallel $\beta$ sheets?

They have better geometry of hydrogen bonding.

What is a 'native conformation'?

The biologically active folding pattern of a protein, which is usually the one with the lowest free energy.

What does the 'funnel' model describe in protein science?

Protein folding, where many unstable conformations collapse into a single, stable folding pattern.

What is the definition of protein denaturation?

The disruption of native conformation resulting in the loss of biological activity.

What is the average molecular weight ($MW$) of an amino acid used to estimate protein size?

$$110$$

Describe the primary and secondary structure of Keratin.

Primary structure has a pseudo-seven repeat (positions $a$ and $d$ are hydrophobic); secondary structure is an $\alpha$-helix.

What is the structural composition of a Keratin coiled-coil?

Two right-handed helicies wrapping around each other in a left-handed fashion.

Describe the primary and secondary structure repeats of Collagen.

Primary structure has repeats of $Gly-X-Y$ (where $X$ is often proline); secondary structure is a left-handed helix with $3$ residues per turn.

What role does Vitamin C play in collagen stability?

It is required by enzymes for the post-translational modification of hydroxyproline and hydroxylysine, which are necessary for stabilizing covalent crosslinks.

What structural elements provide silk with strength and flexibility?

Strength comes from fully extended polypeptide chains ($\beta$-sheets); flexibility comes from hydrogen bonding between strands and van der Waals/hydrophobic interactions between sheets.

Define a Prion disease.

An infectious disease based on the misfolding of a self-protein ($PrP^C$) into a pathological conformation ($PrP^{Sc}$).

What are Disease-Specific Epitopes (DSEs)?

New regions exposed for antibody binding only when a protein misfolds, serving as ideal targets for conformation-specific vaccines.