Lec 7 - speed review

Term / Concept

Definition / Targeted Detail

Shine-Dalgarno Sequence Length & Function

A 6-nucleotide consensus motif located in the 5' UTR upstream of the AUG start codon in prokaryotes. It correctly positions the AUG start codon within the ribosome to initiate translation.

Ferritin mRNA Regulation: Low Iron (Iron Starvation)

Cytosolic aconitase binds a hairpin loop in the 5' UTR of ferritin mRNA near the start site. This physically blocks the ribosomal subunit from scanning, preventing translation so no ferritin protein is produced.

Ferritin mRNA Regulation: Excess Iron (High Iron)

Free iron binds cytosolic aconitase, causing a conformational change that forces it to release the 5' UTR hairpin. This releases translational blockage, allowing ferritin mRNA to be translated into ferritin protein to store iron.

Ferritin Regulation Level: Translation vs. Transcription

Aconitase regulates ferritin strictly at the translational level (by blocking or allowing ribosome scanning on existing mRNA in the cytosol), NOT at the transcriptional level.

eIF2 Role in Translation Initiation

Active eIF2-GTP recruits methionyl-tRNA (initiator tRNA) to the small ribosomal subunit. Upon AUG recognition, eIF2 hydrolyzes GTP to GDP and dissociates as an inactive eIF2-GDP complex.

eIF2B Function & Cellular Abundance

eIF2B is a guanine nucleotide exchange factor (GEF) that reactivates eIF2 by exchanging GDP for GTP. Crucially, eIF2B is present in cells in much lower abundance than eIF2.

Global Translation Repression via eIF2 Phosphorylation

Phosphorylated eIF2 binds tightly to eIF2B and sequesters all available eIF2B into an inactive complex. Because eIF2B is far less abundant, sequestering all eIF2B leaves no free GEF to reactivate the remaining unphosphorylated eIF2-GDP, dramatically shutting down global translation initiation.

Hsp70 Chaperone Mechanism

A monomeric chaperone that acts early (co-translationally) as the polypeptide emerges from the ribosome. It binds directly to exposed short hydrophobic patches and uses ATP hydrolysis cycles to prevent misfolding.

Hsp60 (Chaperonin) Mechanism & Structure

A large multi-subunit barrel-like chamber capped by a GroES cap that acts post-translationally. Misfolded proteins enter the central cavity, where hydrophobic inner walls untangle the protein, allowing it to fold in an isolated chamber away from the crowded cytosol upon ATP hydrolysis.

Chaperone vs. Proteasome Competition

Misfolded proteins with exposed hydrophobic surfaces compete between chaperone-assisted folding and proteasomal degradation. The longer a protein takes to fold, the higher its probability of being targeted to the proteasome for digestion.