The Three-Dimensional Structure of Proteins: Study Notes

Study Guide - Smart Notes

Tailored notes based on your materials, expanded with key definitions, examples, and context.

Recommended Reading: Stryer, Biochemistry, 2nd or 3rd Edition, Chapter 4

Peptide bonds are covalent linkages formed between the α-carboxyl group of one amino acid and the α-amino group of another.
Formation occurs via a condensation reaction, releasing a water molecule:

Peptide bond formation removes the charged α-carboxyl and α-amino groups, resulting in a neutral amide linkage.
The chemical nature of the peptide bond is consistent, regardless of the amino acid side chains involved.

The main chain (or backbone) of a polypeptide is constant, while the side chains (R groups) are variable.
The backbone exhibits a repeating pattern: N–Cα–C–N–Cα–C–...
This regularity is crucial for the formation of higher-order structures.

The peptide bond has partial double bond character due to resonance between the carbonyl oxygen and the amide nitrogen.
This restricts rotation around the C–N bond, making the six atoms of the peptide group (Cα, C, O, N, H, Cα) rigid and planar.
Peptide bonds can exist in cis and trans isomeric forms, but the trans configuration is strongly favored due to reduced steric hindrance.

In the trans configuration, the carbonyl oxygen and the amide hydrogen are on opposite sides of the peptide bond, minimizing steric clashes between side chains.
The cis configuration is rare (except in proline residues) because it increases steric interference.
Steric exclusion principle: two groups cannot occupy the same space at the same time, influencing protein folding and structure.

Primary Structure: The linear sequence of amino acids in a polypeptide chain.
Secondary Structure: Localized folding patterns stabilized by hydrogen bonds (e.g., α-helices, β-sheets).
Tertiary Structure: The overall three-dimensional folding of a single polypeptide chain.
Quaternary Structure: The arrangement and interaction of multiple polypeptide subunits in a protein complex.

Defines the unique sequence of amino acids from the N-terminus (amino end) to the C-terminus (carboxyl end).
Example: Tyr-Gly-Gly-Phe-Leu (YGGFL).
The primary structure determines all higher levels of protein structure and function.
Information for correct folding is encoded in the primary sequence.
Primary structure is often deduced from the gene sequence (codon-to-amino acid relationship).

Example: The peptide YGGFL is the sequence for the opioid peptide enkephalin.

Refers to regular, recurring arrangements of the polypeptide backbone, stabilized by hydrogen bonds.
Common types: α-helix and β-sheet.
Secondary structures are conserved across different proteins and are independent of the specific sequence.
Key rules:
- Optimize hydrogen bonding potential of main-chain carbonyl and amide groups.
- Adopt favored conformations of the polypeptide chain.
Each peptide bond has a hydrogen bond donor (N–H) and acceptor (C=O) group.
Conformations are defined by the phi (φ) and psi (ψ) torsion angles around the Cα–N and Cα–C bonds, respectively.
Not all combinations of φ and ψ are allowed due to steric hindrance; allowed regions are visualized in Ramachandran plots.

Discovered by Linus Pauling in 1951.
Right-handed helix with 3.6 residues per turn.
Stabilized by hydrogen bonds between the carbonyl oxygen of residue n and the amide hydrogen of residue n+4.
Side chains project outward from the helix axis.
Most amino acids can form α-helices, but proline (rigid) and glycine (flexible) are uncommon in helices.
Branched (Val, Thr, Ile) and hydrogen-bonding side chains (Ser, Asp, Asn) are less common due to steric or electrostatic effects.
Helix dipole: the α-helix has a net dipole moment, with partial positive charge at the N-terminus and partial negative at the C-terminus.
Amphipathic helices have hydrophobic and hydrophilic faces, determined by the sequence.

Composed of β-strands aligned side-by-side, forming a sheet-like structure.
Stabilized by hydrogen bonds between backbone atoms of adjacent strands.
Strands can be parallel (same direction) or antiparallel (opposite direction); antiparallel sheets are more stable due to optimal hydrogen bonding geometry.
Mixed β-sheets contain both parallel and antiparallel strands.
β-sheets can be amphipathic, with alternating polar and non-polar residues on opposite faces.

The overall three-dimensional shape of a single polypeptide chain (native conformation).
Stabilized primarily by weak, non-covalent interactions: hydrogen bonds, ionic interactions, van der Waals forces, and hydrophobic interactions.
Disulfide bonds (covalent) may also contribute to stability in some proteins.
Residues distant in primary structure may be close in tertiary structure.
Folding is driven by the search for the lowest free energy state.
Some proteins fold spontaneously; others require molecular chaperones.

Describes the arrangement of multiple polypeptide chains (subunits) in a protein complex.
Subunits may be identical or different and are held together by non-covalent interactions.
Quaternary structure enables cooperative function, stability, and regulation.
Examples: hemoglobin (tetramer), DNA polymerase (multi-subunit enzyme).

Level	Description	Stabilizing Forces	Example
Primary	Linear sequence of amino acids	Covalent peptide bonds	YGGFL (enkephalin)
Secondary	Local folding (α-helix, β-sheet)	Hydrogen bonds	α-helix in myoglobin
Tertiary	3D folding of a single chain	Hydrogen bonds, ionic, hydrophobic, van der Waals, disulfide bonds	Myoglobin
Quaternary	Assembly of multiple chains	Non-covalent interactions, sometimes disulfide bonds	Hemoglobin

Additional info: These notes are based on the provided slides and expanded with standard biochemistry knowledge for clarity and completeness.