Flashcards Chromatin & Post-Translational Events

Nucleosome

DNA wrapped around histone proteins.

Condensed chromatin effect on transcription

Tightly packed chromatin restricts DNA accessibility, leading to decreased transcription.

Chromatin remodelling

Changing the position or packing of nucleosomes to alter DNA accessibility.

SWI/SNF complex function

An ATP-dependent chromatin-remodelling complex that uses ATP hydrolysis to move nucleosomes.

Histone tail charge

Contains positively charged lysine residues that interact with negatively charged DNA.

histone acetylation

Adds acetyl groups to lysine, neutralising positive charge

HAT function

Histone acetyltransferase adds acetyl groups (loosening)

HDAC function

Histone deacetylase removes acetyl groups (condensing)

Effect of histone methylation

Adds methyl groups without neutralising charge, creating binding sites for regulatory proteins.

DNA methylation site in mammals

Commonly occurs at CpG sites, where cytosine is methylated to 5-methylcytosine.

DNA methylation repression pathway

Methylated CpG -> methyl-CpG binding protein -> HDAC -> deacetylation -> condensed chromatin -> gene OFF.

Beta-interferon activation mechanism

Viral infection -> cooperative activator binding -> GCN5 (HAT) -> acetylation -> CBP -> SWI/SNF moves nucleosome -> TATA box exposed -> transcription.

Epigenetic inheritance of histones

Approximately half of parental histones are retained during replication, guiding modification patterns in daughter cells.

Proteome

The complete set of proteins expressed by a cell at a particular time or condition.

Driving force of protein folding

Folding hides hydrophobic residues inside and exposes hydrophilic residues to the aqueous environment.

Molecular chaperones function

Proteins that assist proper folding/refolding and prevent aggregation by binding exposed hydrophobic regions.

HSP70 function

Binds exposed hydrophobic regions early during protein synthesis to prevent aggregation.

HSP60 function

Forms a large barrel-like folding chamber to isolate fully synthesised or misfolded proteins.

Proteasome function

A protein degradation machine that destroys misfolded or unneeded proteins through proteolysis.

Signal sequence

An amino acid sequence encoded within a protein that directs it to a specific cellular destination.

Gated transport

Movement of proteins between the cytosol and nucleus through nuclear pore complexes.

ER signal sequence pathway

Signal peptide -> SRP -> ER membrane -> translocation channel -> signal peptide cleavage.

N-glycosylation

Addition of sugar to the nitrogen atom of asparagine in the ER.

O-glycosylation

Addition of sugar to the oxygen atom of serine or threonine in the Golgi apparatus.

Disulphide bonds formation requirement

Requires an oxidising environment, such as the ER lumen, to form covalent bonds between cysteines.

Insulin post-translational processing

Involves ER targeting, signal cleavage, folding, disulphide bond formation, and proteolysis from proinsulin to mature insulin.

Protein kinase function

An enzyme that uses ATP to add a phosphate group to serine, threonine, or tyrosine residues.

Protein phosphatase function

An enzyme that removes a phosphate group from a protein.

Polyubiquitination function

Attachment of multiple ubiquitin molecules, targeting the protein for proteasomal degradation.

Monoubiquitination function

Attachment of a single ubiquitin molecule, often regulating processes like membrane protein trafficking.

GEF function

Promotes GDP release and GTP binding to activate GTP-binding proteins like Ras.

GAP function

Promotes GTP hydrolysis to inactivate GTP-binding proteins.

Growth factor to MAP kinase pathway sequence

Growth factor -> receptor dimerisation -> autophosphorylation -> Ras-GTP -> RAF -> MEK -> MAP kinase -> nucleus -> gene expression.

Effect of cancer-associated Ras mutations

Impairs GTP hydrolysis, causing Ras to remain active (Ras-GTP) and driving continuous cell division signaling.

Heterochromatin

highly compressed and not transcribed

acetylated

stop condensation, favours transcriptive, gene active (beads on a string)

non-acetylated

favours condensation, represses transcriptive, gene inactive

enhanceosomes

help recruit the transcriptional machinery

protein folding

increase favourable interactions between amino acid residues

majority of regulation occurs when

before translation

Proteolysis

cleavage of peptide bonds by proteases.

Transmembrane transport

Cytosol → ER

Vesicular Transport

ER → Golgi