Lecture 3

Primary → Secondary → Motif (Supersecondary) → Tertiary → Quaternary → Supramolecular complexes.

Linear sequence of amino acids (N-terminal → C-terminal); determines all higher-order folding.

Hydrogen bonds between backbone atoms (N–H → C=O).

Spiral with 3.6 residues/turn; N–H of residue n → C=O of residue n+4; side chains point outward; proline disrupts helix.

β-strands: short, extended. β-sheets: 2+ strands hydrogen-bonded, parallel or antiparallel; side chains alternate above/below plane.

Combination of 2+ secondary structures forming a recurring 3D pattern in multiple proteins, often linked to function.

EF-hand: helix–loop–helix, binds calcium; Zinc-finger: α-helix + 2 β-strands + zinc ion, binds DNA/RNA; β–α–β loop, hairpin (β–β), helix–turn–helix, Greek key; Coiled-coil: 2–4 α-helices coiled, hydrophobic residues stabilize interface; found in structural proteins and TFs.

Overall 3D fold of a polypeptide; stabilized by hydrophobic effect, van der Waals, hydrogen bonds, ionic interactions, disulfide bonds.

Hydrophobic residues cluster in the core, hydrophilic residues exposed; folding driven by entropy increase (water release).

Independent folding units with distinct structure/function; can often function when isolated; modular.

β-barrel of 11 β-sheets around central α-helix; chromophore forms via post-translational modification; α-helices at ends stabilize.

Assembly of multiple polypeptide chains (subunits) into a functional complex; subunits held by noncovalent interactions.

Trimer of HA1 + HA2 subunits; each subunit from HA0 cleavage; noncovalent interactions + disulfide bonds stabilize complex.

Large molecular machines made of multiple proteins (each possibly multimeric), e.g., transcription initiation complex.

Crystallized proteins exposed to X-rays → diffraction → electron density map → atomic model. Limitations: crystallization needed, time-consuming, some proteins difficult to crystallize.

Flash-frozen proteins imaged with electrons; no crystallization; good for large complexes.

Rapid prediction from sequence; predicts interactions; not 100% reliable; complements experimental methods.

Quaternary → subunit → tertiary fold → domains → motifs → secondary structures → primary amino acid sequence.

Primary = shoelace; Secondary = curls/zigzags; Motif = assembled curls; Tertiary = 3D folded shoelace; Quaternary = multiple folded shoelaces forming functional complex.