Translational and Post-Translational Regulation

Vocabulary practice flashcards covering protein folding, chaperone biology, misfolding-related pathology, and post-translational modifications including phosphorylation, acetylation, and ubiquitination.

Primary Structure

The linear sequence of amino acid residues linked by peptide bonds in a polypeptide chain.

Secondary Structure

Local spatial arrangements of the polypeptide backbone, predominantly forming structures such as an $\alpha$ helix or $\beta$ sheet.

Tertiary Structure

The overall three-dimensional folding pattern of a single complete polypeptide chain into its native, functional conformation.

Quaternary Structure

The multi-subunit complex formed by the assembly and spatial arrangement of two or more folded polypeptide chains.

$\alpha$-Synuclein

The specific protein whose misfolding and aggregation is linked to the development of Parkinson's disease.

Prion Protein

The protein responsible for transmissible spongiform encephalopathies, including kuru and Creutzfeldt-Jakob disease (CJD), when misfolded.

Huntingtin

The protein that causes Huntington's disease when mutated and improperly folded.

Superoxide Dismutase

The antioxidant enzyme whose misfolding and aggregation causes familial amyotrophic lateral sclerosis (ALS).

$\alpha 1$-Antichymotrypsin

The protein associated with chronic obstructive pulmonary disease when affected by misfolding defects.

CFTR Protein

The chloride channel protein whose misfolding and trafficking failure causes cystic fibrosis.

Molecular Chaperones

A highly conserved, abundant class of helper proteins found across all organisms that assist newly synthesized or stress-denatured polypeptides in folding into their native functional shapes.

Ferruccio Ritossa

An Italian genetics pioneer who discovered heat shock proteins in the early 1960s after accidentally exposing Drosophila cultures to elevated temperatures and observing novel chromosomal puffs.

Chromosomal Puffs

Visible, decondensed chromosomal regions exhibiting intense transcriptional activity, observed in Drosophila salivary gland polytene chromosomes upon heat shock.

Heat Shock Proteins (HSPs)

Stress-inducible molecular chaperones systematically named after their molecular weight in kilodaltons (e.g., Hsp26 has a molecular weight of $26\,\text{kDa}$).

Hsp70

An essential $70\,\text{kDa}$ molecular chaperone that utilizes ATP hydrolysis to fold and refold the majority of the proteome in both open and closed conformational states.

Post-Translational Modifications (PTMs)

Covalent chemical modifications introduced to amino acid side chains or termini after translation, expanding proteome complexity from $20{,}000\text{--}25{,}000$ genes to over $1{,}000{,}000$ distinct functional proteoforms.

Writer Enzymes

Enzymes that catalyze the covalent addition of post-translational modifications (such as chemical groups, lipids, or polypeptides) onto target proteins.

Eraser Enzymes

Enzymes that catalyze the specific cleavage and removal of post-translational modifications from target proteins.

Reversible PTMs

Modifications that can be dynamically added and removed from a protein by opposing sets of writer and eraser enzymes, such as phosphorylation and acetylation.

Irreversible PTMs

Permanent post-translational alterations to a polypeptide chain that cannot be enzymatically reversed, such as proteolytic cleavage (proteolysis).

Phosphorylation

A prevalent reversible modification where a phosphate group is transferred from the gamma ($\gamma$) position of ATP to an amino acid side chain containing a free hydroxyl ($-\text{OH}$) group.

Protein Kinase

A writer enzyme that catalyzes the transfer of a phosphate group from ATP to specific target substrates, including proteins, lipids, carbohydrates, and nucleotides.

Protein Phosphatase

An eraser enzyme that catalyzes the hydrolytic removal of a covalently attached phosphate group from a phosphorylated amino acid residue.

Serine, Threonine, and Tyrosine

The three canonical eukaryotic amino acids that undergo phosphorylation due to the presence of a reactive hydroxyl ($-\text{OH}$) group in their side chains.

Carboxyl-Terminal Domain (CTD)

The tail domain of RNA polymerase II whose dynamic, reversible phosphorylation state coordinates co-transcriptional RNA capping, splicing, and cleavage/polyadenylation.

Kinome

The complete repertoire of protein kinases encoded within a genome, comprising $518$ kinases in mammals, $122$ in yeast, and over $1000$ in plant genomes.

Small Molecule Kinase Inhibitors (SMKIs)

Pharmaceutical agents typically designed to competitively mimic ATP and block the kinase active site, conventionally designated with names ending in the suffix '-inib' (e.g., Imatinib).

Lysine Acetyltransferases (KATs)

Writer enzymes that catalyze the transfer of an acetyl group from Acetyl-CoA onto specific lysine residues of substrate proteins.

Lysine Deacetylases (KDACs)

Eraser enzymes that remove acetyl groups from acetylated lysine side chains on target proteins.

Sirtuins

A specialized family of lysine deacetylases whose enzymatic deacetylation activity strictly requires $\text{NAD}^+$ as a co-substrate, releasing nicotinamide and connecting cellular metabolism to gene regulation.

Heterochromatin

A densely packed, transcriptionally silent chromatin state associated with hypoacetylated histone tails maintained by deacetylases such as Sir2.

Euchromatin

An open, accessible chromatin conformation that permits active gene transcription, promoted by histone acetyltransferases (such as Sas2 acetylating H4K16).

Bromodomain

A protein structural module that specifically recognizes and binds to acetylated lysine residues, found in chromatin remodelers and transcription factors like SWI/SNF and TFIID.

Ubiquitin

A conserved $76$-amino-acid polypeptide covalently linked to lysine residues of target proteins to direct diverse cellular fates, most notably 26S proteasome-mediated degradation.

Proteolysis

The irreversible hydrolytic breakdown of peptide bonds, serving both regulatory roles and the final clearance step in the protein turnover cycle.