post translational modification Flashcards
Q: What is Post-translational modification (PTM)?
PTM refers to the covalent addition to or cleavage of proteins after their biosynthesis, crucial for regulating cell signaling and enhancing protein diversity beyond the 20 standard amino acids.
Why are PTMs essential for pluripotent stem cells (PSCs)?
PTMs play a critical role in maintaining PSCs’ ability to self-renew and differentiate into any cell type, influencing their fate during development through complex signaling networks.
What are the three germ layers into which PSCs can differentiate, and what do they develop into?
Endoderm: Develops into internal organs (e.g., liver, lungs).
Mesoderm: Forms muscles, bones, and the circulatory system.
Ectoderm: Creates skin and nervous system.
What is the process of cleavage in PTMs?
leavage involves the enzymatic breaking of peptide bonds during processes such as translation, folding, and transport, including the release of functional peptides (e.g., C-peptide from proinsulin).
What are some functional groups commonly added in PTMs?
Phosphorylation: Addition of phosphate groups.
Glycosylation: Addition of sugar moieties.
Acetylation: Addition of acetyl groups.
Methylation: Addition of methyl groups.
What is the significance of phosphorylation in cellular function?
Phosphorylation is one of the most prevalent PTMs, affecting approximately one-third of cellular proteins at any time, and it alters protein conformation, thus regulating enzyme activity (activation or deactivation).
Explain the roles of protein kinases and phosphatases in phosphorylation.
Protein Kinases: Enzymes that catalyze the transfer of phosphate from ATP to target proteins, usually leading to activation. There are 513 characterized kinases, many sharing a homologous catalytic domain.
Phosphatases: Enzymes that remove phosphate groups via hydrolysis, opposing kinases and often playing roles in signaling cascades.
What is glycosylation, and why is it important?
Glycosylation is the covalent attachment of monosaccharides to proteins, aiding in proper protein folding, stability, adhesion, immune responses, hormone function, and embryonic development. It is anchored by dolichol in the membrane.
Describe the process and importance of acetylation.
Acetylation involves adding or removing acetyl groups, often catalyzed by enzymes (acetylases/deacetylases). It significantly impacts gene expression, protein stability, and is predominantly observed at the N-termini of nascent polypeptides.
What is N-terminal acetylation, and how does it function?
N-terminal acetylation is the addition of an acetyl group to the amino terminus of proteins, crucial for protein synthesis, localization, and stability. It is catalyzed by N-terminal acetyltransferases (NATs), and is typically irreversible.
How does lysine acetylation relate to gene expression?
Lysine acetylation is involved in regulating transcription factors (e.g., p53), where the acetylation/deacetylation cycle influences gene activation, affecting cellular responses to various stimuli.
What is the impact of acetylation on histones?
Acetylation of histones neutralises their positive charges, allowing DNA to wrap less tightly, facilitating transcription by promoting access for transcription factors and regulatory proteins, thus enhancing gene expression.
What are potential consequences of high levels of histone acetylation?
Elevated histone acetylation can lead to transcriptional hyperactivity, resulting in overexpression of genes, which may be implicated in various diseases, including cancer.