Controlling protein interaction Flashcards
Give examples of diseases caused by loss of control of proteins?
Cancer
Polycystic kidney disease
Haemophilia
What are the symptoms of haemophilia?
Spontaneous bleeding Prolonged bleeding from cuts Nosebleeds with no known cause Tightness in your joints Internal bleeding
What is a linear enzyme pathway?
One enzyme promotes a response in one other enzyme
What are amplifying enzyme pathways?
One enzyme promotes a response in two enzymes, which trigger two more each
What things can activate or inactivate enzyme?
Allosteric
pH
Covalent
What controls the amount of protein in a cell?
The level of transcription
This is controlled by transcription factors and promoters
What controls the level of mRNA and protein?
Regulating their degradation
How is a protein labelled for degradation?
Protein is ubiquitinated by ubiquotin
Then enters a proteasome
Proteasome and ubiquitin are recycled
Protein fragments released
What is an effector?
A molecule whose binding induces a conformational change that either activates or inhibits
What is the smallest effector?
H+
What is the largest effector?
Another protein
What are competitive inhibitors?
Effectors that bind to the effective site
What are allosteric effectors?
Effectors that bind to regions away from the active site but can still regulate conformation and activity
What may allosteric proteins show?
Multiple ligand binding sites
Demonstrate co-operative ligand binding
What is allosteric regulation?
Production inhibition/ feedback control
Multiple and enzymes are involved
The final end product is an inhibitor of the first enzymes activity
What does product inhibition ensure?
That the activity of an enzyme is reduced when there is sufficient product of the pathway
How is protein kinase A activated by cAMP?
Inactive PKA is bound to inactive catalytic subunits
cAMP binds to the regulatory subunits of PKA
The catalytic subunits are activated and released
What does control by ligand-dependent dissociation of regulatory subunits allow for?
Wide range of outcomes
What expresses cooperative binding?
Haemoglobin
What are some of the functions of interaction domains?
Localisation on other molecules
Recruiting other proteins
Creation of signal hubs
Autoinhibition
What is localisation?
Regulating proteins that don’t have a single function by regulating where they are in the cell
What are protein switches?
Not all protein activities run continuously and are turned on or off
Most protein switches are enzymes that catalyse the hydrolysis of a nucleotide triphosphate
Give examples of protein switches
GTPase
ATPase
How do protein switches cause cancer?
K-Ras GTPase is mutated in ~40 colorectal cancers
Mutated so it cannot be turned off
Describe protein modifications
50% of proteins are covalently modified
Modifications change protein localisation, activity, interaction, degradation
Reversible or irreversible
Give examples of protein modification
Phosphorylation Glycosylation Ubiquitination Sumoylation Disulfide bonds Acetylation Lipidation Methylation Hydroxylation
What is phosphorylation?
Covalent addition of a phosphate to an amino acid side chain
Phosphate derived from adenosine triphosphate
Adds a double negative charge which has dramatic effects on protein conformation
What catalyses phosphorylation?
Kinases
What reverses phosphorylation?
Phosphatases
What are cyclin-dependent kinases?
Essential regulators of cell division
