CH3 | PTMs (2/2) Flashcards
Post-translational modifications (PTMs) are…
alterations in the amino acid sequence of a protein after its synthesis.
PTMs may involve modifying…
the amino acid side chain, terminal amino, or carboxyl group.
PTMs are achieved through…
covalent or enzymatic means.
PTMs influence…
protein structure, stability, activity, cellular localization, or substrate specificity.
PTMs provide…
complexity to the proteome for diverse functions with a limited number of genes.
PTMs can occur…
at any step in the “life cycle” of a protein.
PTMs that occur shortly after translation mediate…
proper protein folding/stability or direct the nascent protein to distinct cellular compartments.
PTMs that occur after folding and localization…
activate/inactivate catalytic activity or influence the biological activity of the protein.
PTMs can also be used to…
get rid of defective proteins or end-of-life proteins.
The human genome comprises approximately…
21,000 genes.
The human proteome is estimated to contain over…
1 million proteins.
The difference in numbers between the genome and proteome demonstrates…
proteome complexity.
The human genome has ~22,000 genes, while the transcriptome has…
~200,000 transcripts.
The increase in numbers from the genome to the transcriptome is due to…
alternative promoters, alternative splicing, and mRNA editing.
The increase in numbers from the transcriptome to the proteome is due to…
post-translational modifications.
How many different types of PTMs are there?
More than 400.
PTMs that involve the addition of chemical groups are…
reversible.
Examples of PTMs that involve the addition of chemical groups include…
hydroxylation, phosphorylation, acetylation, and methylation.
PTMs that involve amino acid modification are…
irreversible.
Examples of PTMs that involve amino acid modification include…
deamidation and eliminylation.
PTMs that involve the addition of complex molecules are…
reversible.
Examples of PTMs that involve the addition of complex molecules include…
AMPylation, ADP-ribosylation, glycosylation, and prenylation.
PTMs that involve the addition of polypeptides are…
reversible.
Examples of PTMs that involve the addition of polypeptides include…
ubiquitylation and UBL-protein conjugation (e.g., SUMO).
PTMs that involve cleavage are…
irreversible.
An example of a PTM that involves cleavage is…
proteolysis.
Phosphorylation involves the addition of…
a phosphate group on serine, threonine, or tyrosine residues.
Phosphorylation converts an uncharged pocket of a protein into…
a negatively charged and hydrophilic protein.
Phosphorylation and dephosphorylation can switch proteins…
on or off.
Phosphorylation has implications in cellular processes such as…
cell cycle, growth, apoptosis, and signal transduction pathways.
The enzyme that adds a phosphate group is called…
kinase.
The enzyme that removes a phosphate group is called…
phosphatase.
Phosphorylation requires what molecule as a phosphate source…
ATP.
Dephosphorylation releases what molecule…
Pi (inorganic phosphate).
Acetylation involves the addition of…
an acetyl group (C2H3O) to a lysine residue.
Acetylation is carried out by enzymes called…
acetyltransferases.
Acetylation neutralizes…
the positive charge on the amino acid residue.
Acetylated proteins cannot be…
ubiquitinated, making them more stable.
Acetylation and deacetylation of histones are a critical part of…
gene regulation.
Histone acetylation causes DNA to become…
accessible, activating the gene.
Deacetylation of histones causes DNA to become…
inaccessible, silencing the gene.
Hydroxylation involves the addition of…
a hydroxyl group (-OH) to proline, lysine, and asparagine.
Hydroxylation is catalyzed by enzymes called…
hydroxylases.
Hydroxylation aids in converting…
hydrophobic compounds into hydrophilic compounds.
Hydroxyproline in collagen plays an important role in…
stabilizing the triple-helix structure of collagen by forming hydrogen bonds.
The hydrogen bonds formed by hydroxyproline in collagen contribute to…
the tensile strength of connective tissues.
Mutations in collagen can lead to connective tissue disorders such as…
Ehlers-Danlos syndrome.
Methylation involves the addition of…
a methyl group to lysine and arginine residues of a protein.
Methylation is achieved by enzymes called…
methyltransferases.
Methylation increases…
the hydrophobicity of the protein.
Methylation can neutralize…
a negative amino acid charge.
Methylation plays a major role in…
gene expression control and cancer by silencing tumor suppressors.
Methylation of DNA and histones causes…
nucleosomes to pack tightly together, making DNA inaccessible and the gene inactive.
DNA methylation…
silences genes.
Demethylation of DNA…
activates genes.
In a normal cell, tumor suppressor genes (TSG) are…
expressed (active transcription).
In a tumor cell, tumor suppressor genes (TSG) are…
silenced (blocked transcription) due to focal hypermethylation.
In a normal cell, oncogenes are…
silenced (blocked transcription).
In a tumor cell, oncogenes are…
expressed (active transcription) due to global hypomethylation.
Glycosylation involves the addition of…
an oligosaccharide ‘glycan’ to either a nitrogen atom (N-linked) or an oxygen atom (O-linked) of asparagine, serine, or threonine residues.
Erythropoietin (EPO) is a glycoprotein hormone that…
stimulates the production of red blood cells.
Glycosylation affects EPO’s…
stability, activity, pharmacokinetics, and pharmacodynamics.
Glycosylation can prolong…
the half-life of EPO in the bloodstream.
Glycosylation can enhance…
EPO’s binding affinity to its receptor.
Differences in the glycosylation pattern of EPO can affect…
its immunogenicity and therapeutic efficacy, with implications for the development of biologic drugs.
Ubiquitination involves the addition of…
a protein - ubiquitin - to the lysine residue of a substrate.
Ubiquitination plays a role in protein degradation by…
targeting the protein to the proteasome for degradation into small peptides.
Ubiquitination plays a role in protein trafficking by…
targeting proteins to specific subcellular compartments, such as targeting membrane proteins for internalization and lysosomal degradation or cytoplasmic proteins for transport to the nucleus.
Ubiquitination plays a role in protein signaling by…
activating or inhibiting the enzymatic activity of some proteins or promoting their interaction with other proteins.
Ubiquitination is involved in cellular processes such as…
DNA repair, cell cycle regulation, and immune response.
Ubiquitination is involved in the regulation of…
the tumor suppressor protein p53.
Proteolysis can remove…
regulatory proteins when they are not needed.
Proteolysis can transform proteins…
from the dormant into the biologically active state.
An example of a protein that undergoes proteolysis to become active is…
insulin.
The first step in insulin processing involves…
the removal of the signal sequence from preproinsulin to produce proinsulin.
Proinsulin contains…
an A chain, a B chain, and a C-peptide.
The second step in insulin processing involves…
the removal of the C-peptide from proinsulin to produce insulin.
The active form of insulin contains…
an A chain and a B chain linked by disulfide bonds.
The cleavage site for insulin processing critically includes…
a lysine residue.
Deamidation involves the removal of…
amide groups in asparagine or glutamine, converting them to aspartic or glutamic acid.
Deamidation is catalyzed by enzymes called…
deamidases.
α-crystallin, a small protein in the eye’s lens, aids in…
proper protein folding and shape maintenance.
α-crystallin contains several asparagine residues that are susceptible to…
deamidation over time, particularly in the aging lens.
Deamidation of α-crystallin can affect…
its structure and function.
Deamidation of α-crystallin has been linked to…
the formation of cataracts, a common age-related eye disorder.
