membrane structure and function Flashcards
- Describe the role of cholesterol in modulating membrane protein function.
Answer: Cholesterol can regulate membrane proteins both generally by altering membrane fluidity and specifically by binding within protein structures. Example: it binds between TM1 and TM6 of the dopamine transporter, preventing TM1 movement, thus inhibiting dopamine release into the cell.
- What are lipid rafts, and what is their function in cell signaling?
Answer: Lipid rafts are microdomains enriched in cholesterol and sphingolipids. They organize signaling molecules, concentrating receptors and signaling proteins for efficient signal transduction.
- Compare the functions and energy requirements of flippases, floppases, and scramblases.
Answer:
Flippases (P-type ATPases): Move lipids from outer to inner leaflet (ATP required).
Floppases (ABC transporters): Move lipids from inner to outer leaflet (ATP required).
Scramblases: Bidirectional, randomize lipid distribution (no ATP); active during apoptosis or signaling.
- In the bacterial flippase PglK mechanism, what drives lipid flipping?
Answer: ATP hydrolysis drives conformational changes in PglK, exposing a V-shaped cavity that flips the lipid-linked oligosaccharide from cytoplasmic to periplasmic side.
- Identify the sites of phospholipid cleavage for the major phospholipases A2, C, and D.
Answer:
Phospholipase A2: Cleaves at the sn-2 position, releasing arachidonic acid.
Phospholipase C: Cleaves between glycerol and phosphate, releasing IP3 and DAG.
Phospholipase D: Cleaves after phosphate group, producing phosphatidic acid and alcohol.
How do phospholipases contribute to the production of arachidonic acid and downstream lipid signaling?
Answer:
PLA2 releases arachidonic acid directly.
PLC indirectly contributes by generating DAG, which can be converted to arachidonic acid via DAG lipase.
Explain the signaling cascade initiated by PIP2 hydrolysis.
Answer:
PIP2 is cleaved by PLC into DAG and IP3.
IP3 diffuses to the ER and opens Ca²⁺ channels.
DAG remains in membrane and activates protein kinase C (PKC), which phosphorylates downstream proteins.
What is the function of PIP2 in membrane protein regulation?
Answer: PIP2, being negatively charged, can bind to positively charged residues of proteins (e.g., serotonin transporter) and regulate their conformation/function/ binding & transporter actvitiy.
List the major bioactive lipids derived from arachidonic acid and give an example of each class.
Answer:
Prostaglandins: e.g., Prostaglandin E2
Leukotrienes: e.g., Leukotriene B4
Endocannabinoids: e.g., Anandamide
How does N-arachidonyl glycine (NAGly) contribute to analgesia and what does it target?
Answer:
NAGly modulates membrane protein activity and inhibits GlyT2 (glycine transporter), increasing glycinergic signaling and reducing pain transmission.
Oleoyl-D-lysine is a potent GlyT2 inhibitor developed from NAGly structure.
What is the importance of identifying the binding pocket of Oleoyl-D-lysine on GlyT2 in drug development?
Answer: Structural identification enables structure-based drug design for more potent and selective analgesics.
Q5. Discuss how arachidonic acid is produced and its biological significance.
A5. Arachidonic acid is produced from membrane phospholipids through the action of phospholipase A2. It serves as a precursor to several important signaling molecules, including prostaglandins (regulating inflammation and blood flow), leukotrienes (modulating immune responses), and endocannabinoids (affecting pain perception and neuromodulation).
Q6. How does PIP2 regulate membrane protein activity?
A6. PIP2, found on the intracellular leaflet of the membrane, binds to positively charged residues of membrane proteins (e.g., serotonin transporter), modulating their activity. This interaction affects protein conformation and function, contributing to signal regulation.
. Explain the significance of Oleoyl-D-lysine in drug discovery.
A7. Oleoyl-D-lysine is a potent and selective inhibitor of GlyT2, a glycine transporter. It enhances glycine neurotransmission in the spinal cord, offering analgesic effects. Its defined binding site enables structure-based drug discovery for chronic pain therapeutics.
