Lecture 7: Membrane Protein Function Flashcards
(46 cards)
How are metabolic pathways and gene expression initiated and what is most essential for this response
The binding of signalling molecules to their receptors initiates. Proteins are essential for carrying out response`
What are two classes of hormones and which ones use GCPRs
nonsteroidal and steroidal hormones; steroidal hormones can diffuse accross whereas nonsteroidal use signalling methods such as GCPRs
Describe signal transmission stepwise
1) signal
2) reception by receptor, typically integrl membrane protein
3) transduction and amplification through secondary messenger such as cAMP
4) Response
5) Termination
Define GCPRs
Class f receptors that are part of a super-family of membrane proteins
They contain 7TM segments, can bind many different ligands
release G-proteins upon binding due to a conformational change
Five examples of natural GCPR systems
- serotonin
- epinephrine
- prostaglandins
- dopamine
- psilocin
Three examples of synthetic GCPR systems
- morphine
- histamine
- LSD
What influences binding affinity
noncovalent interactions between the amino acids side chains and the molecules functional groups
How can non-covalent interactions between biomolecules be compared
by looking at binding affinities
What are Kd values and what do they mean
Kd = dissociation constants
lower Kd = stronger binding
How is a dissociation constant calculated
Kd= (A)(B)/(AB)
where
A= #receptors
B= #ligands
AB= #receptor-ligand interactions
or
Kd = Kon (rate binding)/Koff (rate unbinding)
Describe two important properties of binding
1) Saturable
- there is an upper limit to the amount of binding that can occur
2) Based on stoichiometry
- occurs as a 1:1 interaction
Describe how ligand binding induces conformational changes in the B2 AD Receptor
1) ligand binding induces small changes in TM5 on the extracellular side
2) a 14A movement of TM6 (swings outward, inside cell) transmits signal inside
3) The major conformational changes in TM6 promote Ga activation
Describe epi signalling pathway stepwise
1) Epinephrine binding induces a conformational change, releasing Ga subunit in the GTP bound state
2) Adenylyl cyclase is activated and produces cAMP from ATP
3) cAMP activates PKA
4) PKA phosphorylates Ca2+ channels to send signals
What is PKA
Protein kinase A, a tranferase that can phosporylate and activate/inactivate other enzymes
Describe epi pathway termination stepwise
1) Turn off PKA
2) cAMP to AMP
3) GaGTP cut to GDP (GTP hydrolysis)
4) epinephrine binding blocked
What can regulate the GPCR signalling cascade
PTMs, disrupting binding interactions, metabolizing molecules, protein degradation
What is the one most effective way to turn off epinephrine signalling
Unbind epinephrine/ block epinephrine binding site
Define Ras Proteins
Members of the superfamily of small GTPases that bind and hydrolyze GTP where the hydrolysis results in a conformational change in the switch I and switch II motifs
What can occur from defects in GTP hydrolysis
uncontrolled signalling and cancer
Define Enzyme-linked Receptors
Receptors with a single TM segment whose activation leads to autophosphorylation or phosphorylation by tyrosine kinases
Two examples of enzyme-linked receptors
insulin, epidermal growth factor (EGF)
Describe phospholipid-mediated signalling
What are two examples ?
phospholipases hydrolyze phospholipids to produce other 2s messengers
eicosanoid and AKT signalling
What two 2nd messengers lead to the release of calcium from the ER
DAG and IP3
Define Ion Channel Proteins
Membrane transporters that facilitate diffusion
