BIOC0005 WEEK 15 EXAM QUESTIONS AND ANSWERS
WITH COMPLETE SOLUTIONS
different types of post translatinal modifiations?
- with disuphite bond formation, it happens when the cisteines residues are oxidated
hence lose electron hence form a disulfite bond. this specific modification is what
indicates to the cell that there is oxidative stress happening!
- most cases tho, you have small molecules which are attached to the proetins eg:
phosphates, methyl groups, acetyl groups, sugars, ubiquitin molecule, fats or hydroxyls
- remeber usually there are specific enzymes that are responsible for attaching said
modificaions to the substrate protein eg protein kinases, histidne transferases...
- note often the binding of an enzyme to its substrae involves a bulky substance like
ubiquitin.
what are the functions of post translationa modifications in cells? and examples
of PTM?
- 1. Creation of Docking Sites in Signaling Complexes: PTMs such as phosphorylation
create specific sites on proteins that act as docking points for other proteins
ESPECIALLY signaling molecules. Example: Phosphorylated tyrosines can serve as
docking sites for proteins containing SH2 domains, facilitating signal transduction
pathways.
- 2. Activation/Inhibition of Enzymatic Activities: PTMs can alter enzyme conformation,
either activating or inhibiting their catalytic activity. note most enzymes are in inactive
,form. Example: Phosphorylation can activate kinases or inhibit phosphatases, thereby
regulating metabolic and signaling pathways.
- 3. Modification of Subcellular Localization: PTMs can influence protein localization
within different cellular compartments. Example: Phosphorylation, ubiquitination, or
acetylation can cause proteins to move to the nucleus, mitochondria, or plasma
membrane, impacting their function based on their new location. eg of how this could
work is editing the nuclear localisation sequence and make it functional
- 4. Targeting for Degradation: PTMs, particularly ubiquitination, signal proteins for
degradation by the proteasome or lysosome.
Example: Ubiquitination often marks proteins for proteasomal degradation, regulating
protein turnover and maintaining cellular homeostasis.
-- pic just shows examples of PTMs
what are protein domains which recognise modified protein sequences?
- SH2 (Src Homology 2) Domain: Binds to phosphorylated tyrosine residues.
Commonly found in signaling proteins, SH2 domains are crucial for the recruitment and
assembly of signaling complexes. The binding specificity is determined by residues
immediately downstream of the phosphorylated tyrosine (pY).
- PTB (Phosphotyrosine Binding) Domain
Function: Binds to phosphorylated tyrosine residues, often in NPxY
motifs. Significance: PTB domains are involved in signal transduction and the
regulation of receptor endocytosis. They can also bind to unphosphorylated tyrosine
residues in certain contexts.
,- Chromodomain: Recognizes methylated lysine residues on histones and other
proteins. Chromodomains are involved in the regulation of chromatin structure and gene
expression. They play a role in reading the histone code, which is crucial for epigenetic
regulation.
- Bromodomain: Recognizes acetylated lysine residues.
Significance: Bromodomains are involved in the regulation of transcription by
recognizing acetylated histones, which is a marker of active gene transcription.
Molecular Mechanisms of Protein Phosphorylation/Dephosphorylation
- 1. Phosphorylation: Phosphorylation typically occurs on amino acids with hydroxyl
groups, such as serine, threonine, and tyrosine.
-- Protein Kinases: These enzymes catalyze the transfer of a phosphate group from
ATP to the hydroxyl group of the target amino acid.
-- Serine/Threonine Kinases: Phosphorylate serine or threonine residues. Examples
include PKA (Protein Kinase A), PKC (Protein Kinase C), and MAPKs (Mitogen-
Activated Protein Kinases).
-- Tyrosine Kinases: These specifically target tyrosine residues. They are crucial in
signaling pathways involving receptor tyrosine kinases (RTKs) and non-receptor
tyrosine kinases like Src.
-- Activation/Inactivation of Enzymes: Phosphorylation can alter enzyme
conformation, either activating or inhibiting their activity.
-- Creation of Docking Sites: Phosphorylated residues, particularly tyrosines, can
create docking sites for proteins with SH2 or PTB domains, facilitating signal
transduction.
, - 2. Dephosphorylation: The removal of phosphate groups also occurs on serine,
threonine, and tyrosine residues.
-- Protein Phosphatases: Catalyze the removal of phosphate groups, reversing the
action of kinases.
-- [Serine/Threonine Phosphatases: Include enzymes like PP1, PP2A, and PP2B
(calcineurin), which dephosphorylate serine or threonine residues. Tyrosine
Phosphatases: Examples include PTP1B and SHP2, which specifically remove
phosphates from tyrosine residues.] [don't have to know]
-- Termination/Modulation of Signals: Dephosphorylation often serves to terminate
signaling events or modulate their intensity, preventing overactive signaling.
-- Restoration of Protein Function: In some contexts, dephosphorylation can restore
the function of proteins that are inactivated by phosphorylation.
Protein phosphorylation: creation of docking sites for signal transduction
- The binding of a ligand (e.g., a growth factor) to the extracellular domain of receptor
tyrosine kinases (RTKs) induces receptor dimerization. This is depicted in the left part of
the image where the receptors are shown coming together.
- Once dimerized, the intracellular kinase domains of the receptors become activated.
This leads to transphosphorylation, where each kinase domain phosphorylates tyrosine
residues on the opposite receptor's intracellular tail. The diagram shows ATP being
used to transfer phosphate groups to these tyrosine residues.
- Creation of Docking Sites: The phosphorylated tyrosine residues (phospho-tyrosines)
serve as docking sites for downstream signaling molecules that contain specific
recognition domains such as SH2 (Src Homology 2) domains or PTB (Phosphotyrosine
WITH COMPLETE SOLUTIONS
different types of post translatinal modifiations?
- with disuphite bond formation, it happens when the cisteines residues are oxidated
hence lose electron hence form a disulfite bond. this specific modification is what
indicates to the cell that there is oxidative stress happening!
- most cases tho, you have small molecules which are attached to the proetins eg:
phosphates, methyl groups, acetyl groups, sugars, ubiquitin molecule, fats or hydroxyls
- remeber usually there are specific enzymes that are responsible for attaching said
modificaions to the substrate protein eg protein kinases, histidne transferases...
- note often the binding of an enzyme to its substrae involves a bulky substance like
ubiquitin.
what are the functions of post translationa modifications in cells? and examples
of PTM?
- 1. Creation of Docking Sites in Signaling Complexes: PTMs such as phosphorylation
create specific sites on proteins that act as docking points for other proteins
ESPECIALLY signaling molecules. Example: Phosphorylated tyrosines can serve as
docking sites for proteins containing SH2 domains, facilitating signal transduction
pathways.
- 2. Activation/Inhibition of Enzymatic Activities: PTMs can alter enzyme conformation,
either activating or inhibiting their catalytic activity. note most enzymes are in inactive
,form. Example: Phosphorylation can activate kinases or inhibit phosphatases, thereby
regulating metabolic and signaling pathways.
- 3. Modification of Subcellular Localization: PTMs can influence protein localization
within different cellular compartments. Example: Phosphorylation, ubiquitination, or
acetylation can cause proteins to move to the nucleus, mitochondria, or plasma
membrane, impacting their function based on their new location. eg of how this could
work is editing the nuclear localisation sequence and make it functional
- 4. Targeting for Degradation: PTMs, particularly ubiquitination, signal proteins for
degradation by the proteasome or lysosome.
Example: Ubiquitination often marks proteins for proteasomal degradation, regulating
protein turnover and maintaining cellular homeostasis.
-- pic just shows examples of PTMs
what are protein domains which recognise modified protein sequences?
- SH2 (Src Homology 2) Domain: Binds to phosphorylated tyrosine residues.
Commonly found in signaling proteins, SH2 domains are crucial for the recruitment and
assembly of signaling complexes. The binding specificity is determined by residues
immediately downstream of the phosphorylated tyrosine (pY).
- PTB (Phosphotyrosine Binding) Domain
Function: Binds to phosphorylated tyrosine residues, often in NPxY
motifs. Significance: PTB domains are involved in signal transduction and the
regulation of receptor endocytosis. They can also bind to unphosphorylated tyrosine
residues in certain contexts.
,- Chromodomain: Recognizes methylated lysine residues on histones and other
proteins. Chromodomains are involved in the regulation of chromatin structure and gene
expression. They play a role in reading the histone code, which is crucial for epigenetic
regulation.
- Bromodomain: Recognizes acetylated lysine residues.
Significance: Bromodomains are involved in the regulation of transcription by
recognizing acetylated histones, which is a marker of active gene transcription.
Molecular Mechanisms of Protein Phosphorylation/Dephosphorylation
- 1. Phosphorylation: Phosphorylation typically occurs on amino acids with hydroxyl
groups, such as serine, threonine, and tyrosine.
-- Protein Kinases: These enzymes catalyze the transfer of a phosphate group from
ATP to the hydroxyl group of the target amino acid.
-- Serine/Threonine Kinases: Phosphorylate serine or threonine residues. Examples
include PKA (Protein Kinase A), PKC (Protein Kinase C), and MAPKs (Mitogen-
Activated Protein Kinases).
-- Tyrosine Kinases: These specifically target tyrosine residues. They are crucial in
signaling pathways involving receptor tyrosine kinases (RTKs) and non-receptor
tyrosine kinases like Src.
-- Activation/Inactivation of Enzymes: Phosphorylation can alter enzyme
conformation, either activating or inhibiting their activity.
-- Creation of Docking Sites: Phosphorylated residues, particularly tyrosines, can
create docking sites for proteins with SH2 or PTB domains, facilitating signal
transduction.
, - 2. Dephosphorylation: The removal of phosphate groups also occurs on serine,
threonine, and tyrosine residues.
-- Protein Phosphatases: Catalyze the removal of phosphate groups, reversing the
action of kinases.
-- [Serine/Threonine Phosphatases: Include enzymes like PP1, PP2A, and PP2B
(calcineurin), which dephosphorylate serine or threonine residues. Tyrosine
Phosphatases: Examples include PTP1B and SHP2, which specifically remove
phosphates from tyrosine residues.] [don't have to know]
-- Termination/Modulation of Signals: Dephosphorylation often serves to terminate
signaling events or modulate their intensity, preventing overactive signaling.
-- Restoration of Protein Function: In some contexts, dephosphorylation can restore
the function of proteins that are inactivated by phosphorylation.
Protein phosphorylation: creation of docking sites for signal transduction
- The binding of a ligand (e.g., a growth factor) to the extracellular domain of receptor
tyrosine kinases (RTKs) induces receptor dimerization. This is depicted in the left part of
the image where the receptors are shown coming together.
- Once dimerized, the intracellular kinase domains of the receptors become activated.
This leads to transphosphorylation, where each kinase domain phosphorylates tyrosine
residues on the opposite receptor's intracellular tail. The diagram shows ATP being
used to transfer phosphate groups to these tyrosine residues.
- Creation of Docking Sites: The phosphorylated tyrosine residues (phospho-tyrosines)
serve as docking sites for downstream signaling molecules that contain specific
recognition domains such as SH2 (Src Homology 2) domains or PTB (Phosphotyrosine
