Molecular Mechanisms of Membrane Proteins Flashcards
- What are the two types of membrane proteins?
Answer:
Integral proteins – Span the membrane (e.g., channels, transporters, GPCRs).
=> Span across the entire lipid bilayer
Have parts exposed to both extracellular and intracellular environments
Peripheral proteins – Attach to one side of the membrane (e.g., scaffold proteins).
==> Do not span the lipid bilayer
Loosely attached to the inner or outer surface of the membrane
Often interact with integral proteins or lipid headgroups
What are the six main functions of membrane proteins?
Answer:
Transport – Move solutes across the membrane (e.g., channels, pumps, transporters).
Signal Transduction – Receptors activate intracellular signaling (e.g., GPCRs).
Cell-to-Cell Adhesion – Connect cells together (e.g., tight junctions, connexins).
Cytoskeletal Attachment – Anchor membrane proteins to the cytoskeleton.
Enzymatic Activity – Membrane-bound enzymes catalyze reactions.
Cell Recognition – Identify self vs. foreign (e.g., immune system).
What is the difference between channels, transporters, and pumps?
Answer:
Channels – Provide an open pore, allow passive flow of ions down electrochemical gradient.
Transporters – Undergo conformational change to move solutes across the membrane.
Pumps – Use ATP to move ions against their gradient (e.g., Na+/K+ ATPase).
How do passive transporters work?
Answer:
No energy required.
Solutes move down their electrochemical gradient.
Example: GLUT2 (Glucose Transporter) → Moves glucose into cells when concentrations are high.
What are primary active transporters? Give an example.
Answer:
Use ATP hydrolysis to transport solutes against their gradient.
Example: Na+/K+ ATPase pumps 3 Na+ out, 2 K+ in, maintaining resting membrane potential.
What are secondary active transporters?
Answer:
Use pre-existing ion gradients instead of ATP.
Example: Na+/Glutamate Transporter (SLC1A) – Uses Na+ gradient to pull glutamate into neurons.
What are Solute Carrier (SLC) Transporters?
Answer:
A large family of non-ATP-dependent transporters.
Includes facilitated diffusion carriers (e.g., GLUT) and secondary active transporters (e.g., neurotransmitter transporters).
How do neurotransmitter transporters work?
Answer:
Use Na+-coupled secondary active transport to clear neurotransmitters from the synaptic cleft.
Examples:
Glutamate Transporter (SLC1A) – Removes excess glutamate from synapses.
Dopamine/Serotonin/GABA Transporters (SLC6 Family) – Control neurotransmitter reuptake.
How do ATP-Binding Cassette (ABC) Transporters work?
Answer:
Use ATP to move solutes across membranes.
Example: CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) – A Cl- channel regulated by ATP binding.
What are the two main types of ion channels?
Answer:
Ligand-gated ion channels (LGICs) → Open when a ligand (e.g., neurotransmitter) binds.
Voltage-gated ion channels → Open when membrane potential changes.
How do ligand-gated ion channels (LGICs) function?
Answer:
Ligand binds to extracellular receptor site → conformational change opens channel.
Example: NMDA receptors (bind glutamate, allow Ca2+ influx).
How do voltage-gated ion channels work?
Answer:
Open in response to changes in membrane potential.
Example: Na+ and K+ channels in neurons control action potentials.
What are mechanosensitive ion channels?
Answer:
Open in response to membrane stretch or pressure.
Example: Stretch-activated K+ channels in sensory neurons.
What is the role of Na+/K+ ATPase in ion balance?
Answer:
Pumps 3 Na+ out, 2 K+ in, keeping intracellular Na+ low and K+ high.
Helps maintain resting membrane potential and osmotic balance.
How do glutamate transporters maintain neurotransmitter balance?
Answer:
Use Na+ gradient to remove glutamate from synapses.
Prevent excitotoxicity (too much glutamate can kill neurons).
Work alongside Na+/K+ ATPase.
What are dual-function transporters/channels?
Answer:
Some transporters also act as ion channels.
Example: Glutamate transporters also allow Cl- to pass for charge neutralization.
lutamate transporter a carrier?
✅ Yes.
The glutamate transporter (e.g., EAAT2) is a secondary active transporter → it’s a carrier, which means it:
Binds glutamate + ions on one side
Undergoes a conformational change
Releases glutamate on the other side
This is slow and specific — classic carrier behavior.
It uses:
3 Na⁺ in
1 H⁺ in
1 K⁺ out → to drive glutamate uptake against its concentration gradient
🧪 2. What about the Cl⁻ channel part?
Surprisingly, yes — some glutamate transporters also act as an ion channel for chloride (Cl⁻).
This Cl⁻ conductance is independent of glutamate transport.
It’s passive — Cl⁻ just flows down its electrochemical gradient
It does not require ATP or Na⁺ cotransport
💡 Think of it as a “side activity” — like a door that occasionally opens for Cl⁻ while the main business of moving glutamate still goes on through a separate mechanism.
⚖️ Why does this dual function matter?
The Cl⁻ conductance may help balance charge movement caused by the electrogenic glutamate transport.
It might also modulate neuronal excitability and osmotic stability.
What are the non-transport functions of membrane proteins?
Answer:
Anchor to intracellular cytoskeleton like actin or ECM via integrins
=> maintain cell shape and respond to mechanical signals.
Scaffold proteins – Link cytoskeleton to membrane// also like to cluster receptors and enzymes together to enhance efficiency
Cell-to-cell adhesion – Tight junctions, connexins. (maintains tissue structure and communication (important in epithelial layers))
Enzymatic activity – some membrane proteins are enzymes themselves or part of enzyme complexes
e.g. enzyme may degrade a neurotransmitter right after it activates a GPCR to terminate the signal.
Cell recognition – Immune system proteins identify foreign vs. self-cells.
underlies immune recognition (e.g., MHC molecules) and cell sorting in development.
How do GPCRs (G-Protein Coupled Receptors) work?
Answer:
Ligand binds extracellular domain → Conformational change.
GDP is replaced by GTP, activating G-protein.
G-protein triggers intracellular signaling (e.g., activates second messengers).
Example: β-Adrenergic receptor (activated by adrenaline).
What happens when membrane transporters fail?
Answer:
GLUT2 mutation → Fanconi-Bickel syndrome (glycogen storage disease).
CFTR mutation → Cystic fibrosis (thick mucus due to Cl- transport failure).
Na+/K+ ATPase dysfunction → Neurological & cardiac issues.
How do membrane proteins regulate osmotic balance?
Answer:
Na+/K+ ATPase maintains ion balance.
Cl- transporters regulate water movement.
Aquaporins allow water flow across membranes.
Two Main Functions of Receptors:
- Signal transduction via GPCRs (G-protein-coupled receptors)
A ligand (e.g., hormone, neurotransmitter) binds outside the cell.
The receptor activates G-proteins inside the cell (see the blue G).
This triggers a cascade of intracellular events, like producing second messengers (e.g., cAMP).
⟶ Example: adrenaline binding to β-adrenergic receptors.
- Opening ion channels (Ligand-gated ion channels)
A ligand binds directly to a channel protein, causing it to open.
This allows ions (Na⁺, K⁺, Ca²⁺, Cl⁻) to flow through, changing the electrical state of the cell.
⟶ Example: acetylcholine at the neuromuscular junction opens Na⁺ channels.
