01 / 20

Membrane Proteins
Channels, Transporters, Receptors

Explore the three major classes of membrane proteins that control what enters and exits cells, and how cells communicate with their environment.

Biochemistry

Why Membrane Proteins Matter

The phospholipid bilayer is selectively permeable: small, nonpolar molecules (like \( \text{O}_2 \) and \( \text{CO}_2 \)) slip through easily, but ions, glucose, and signaling molecules cannot. Membrane proteins solve this problem by providing controlled pathways and information relays across the membrane.

The Lipid Bilayer Barrier

+ ✕ Glucose Extracellular Intracellular Channel Protein

The Three Major Classes

Ion Channels
Passive pores that allow specific ions to flow down their concentration gradient. No energy required.
Transporters
Proteins that bind solutes and undergo conformational changes. Can move molecules against their gradient (active transport).
Receptors
Detect extracellular signals (ligands) and trigger intracellular responses without transporting the signal molecule itself.

Ion Channels: Passive Gated Pores

Voltage- gated
\( \text{Na}^+ / \text{K}^+ \)
 Ligand- gated
\( \text{Ca}^{2+} \)
 Mechano- sensitive
\( \text{K}^+ \)
All channels: passive, selective, rapid (\( 10^6 \text{–} 10^8 \text{ ions/sec} \))

Transporters: Conformational Carriers

Unlike channels, transporters bind their substrate and undergo a conformational change to shuttle it across the membrane. This makes them slower but capable of moving solutes against their gradient.

Passive (Uniporter)
Moves one solute down its gradient. Example: GLUT1 glucose transporter.
Active (Primary)
Uses ATP hydrolysis directly. Example: \( \text{Na}^+/\text{K}^+ \) ATPase pumps \( 3 \text{ Na}^+ \) out, \( 2 \text{ K}^+ \) in per ATP.
Active (Secondary)
Couples uphill transport of one solute to downhill flow of another (symport or antiport).

The \( \text{Na}^+/\text{K}^+ \) ATPase Cycle

\( \text{Na}^+/\text{K}^+ \)
ATPase
 Extracellular Intracellular
\( \text{Na}^+ \)
\( \text{Na}^+ \)
\( \text{Na}^+ \)
\( 3 \text{ Na}^+ \text{ out} \)
\( \text{K}^+ \)
\( \text{K}^+ \)
\( 2 \text{ K}^+ \text{ in} \)
\( \text{ATP} \rightarrow \text{ADP} + \text{P}_i \)

Receptors: Signal Without Transport

Receptors do not move the signaling molecule across the membrane. Instead, a ligand binds the extracellular domain and triggers a conformational change that activates an intracellular response.

GPCRs
7-transmembrane helix. Activate G-proteins inside the cell. Largest receptor superfamily.
Receptor Tyrosine Kinases
Ligand binding causes dimerization and autophosphorylation of tyrosine residues.
Ligand-Gated Ion Channels
Function as both receptor and channel: ligand binding opens the pore directly.

GPCR Signaling Cascade

Ligand binds GPCR GPCR changes shape G-protein
\( \text{GDP} \rightarrow \text{GTP} \)
 Effector Enzyme e.g. Adenylyl cyclase Second Messenger cAMP produced Cellular Response AMPLIFICATION

Channel vs Transporter: The Key Distinction

Feature Ion Channel Transporter
Mechanism Open pore (aqueous) Bind, conformational change, release
Rate \( 10^6 \text{–} 10^8 \) ions/sec \( 10^2 \text{–} 10^4 \) molecules/sec
Direction Down gradient only (passive) Down or against gradient
Energy None (uses \( \Delta G \) of gradient) None (passive) or ATP / ion gradient (active)
Selectivity Size/charge filter Binding-site specificity
Saturation No (linear with gradient) Yes (Michaelis-Menten kinetics)

Three Classes Compared

Property Channel Transporter Receptor
Moves solute? Yes (passive) Yes (passive or active) No
Binds substrate tightly? No Yes Yes (ligand)
Conformational change? Gate open/close Major Major
Output Ion flux Solute translocation Signal cascade
Example \( \text{K}^+ \) channel \( \text{Na}^+/\text{K}^+ \) ATPase Insulin receptor

How to Classify a Membrane Protein

1
Does it move a solute across the membrane? If no, it is a receptor.
2
Does it form an open pore? If yes, it is an ion channel (passive, very fast).
3
Does it bind the solute and change shape? If yes, it is a transporter.
4
Does it require ATP or an ion gradient? If so, it is an active transporter. If not, it is a passive transporter (facilitated diffusion).

Example 1: GLUT1 Glucose Transporter

Outward-open Glc flip Inward-open Glc Extracellular (high [Glucose]) Intracellular (low [Glucose]) Passive Transporter

Example 2: SGLT1 Sodium-Glucose Symporter

\( \text{Na}^+ \)
\( \text{Na}^+ \text{ (downhill)} \)
 Glc Glucose (uphill) Both enter cell Secondary Active Symporter
\( \text{High } [\text{Na}^+] \)
\( \text{Low } [\text{Na}^+] \)

Example 3: Insulin Receptor (RTK)

1
Insulin binds the extracellular domain of the receptor, causing two receptor subunits to dimerize.
2
Autophosphorylation: each subunit phosphorylates tyrosine residues on the other (trans-phosphorylation).
3
Signal relay: phosphotyrosines recruit adaptor proteins (e.g., IRS-1), triggering the PI3K/Akt pathway.
4
Cellular response: GLUT4 vesicles fuse with the plasma membrane, increasing glucose uptake.

Common Mistakes

✕ Channels use ATP
Channels are always passive. They harness the electrochemical gradient, not ATP. Only active transporters use ATP.
✕ Receptors transport ligands
Receptors detect signals and relay them. The ligand stays on the outside (or is internalized separately by endocytosis).
✕ Facilitated = active
Facilitated diffusion uses transporters but moves solutes down their gradient. It is still passive: no energy input.

Question 1 of 5

Which of the following best describes the function of an ion channel?

Question 2 of 5

The \( \text{Na}^+/\text{K}^+ \) ATPase moves \( 3 \text{ Na}^+ \) out and \( 2 \text{ K}^+ \) in per cycle. This makes it:

Question 3 of 5

SGLT1 transports glucose into intestinal cells by coupling it to \( \text{Na}^+ \) movement. This is an example of:

Question 4 of 5

A GPCR differs from a transporter because the GPCR:

Question 5 of 5

Which statement correctly distinguishes facilitated diffusion from active transport?