What the exam asks
- Explain why a particular ligand binds to a cell-surface receptor versus an intracellular receptor based on polarity, charge, and membrane permeability.
- Describe how ligand binding alters the conformation (shape) of a receptor’s intracellular domain to initiate transduction.
- Interpret visual models of G protein-coupled receptors (GPCRs), ligand-gated ion channels, second messengers, and phosphorylation cascades.
- Explain how enzymatic relays and second messengers amplify a single extracellular signal into a massive cellular response.
Core ideas
1. Reception: Ligands and receptor location
Signal transduction links reception (detecting a signaling molecule) to transduction (relaying and amplifying the message inside the cell) and finally to a cellular response (such as gene expression, enzyme activation, or apoptosis).
A signaling molecule, called a ligand, binds noncovalently and reversibly to a specific ligand-binding domain on a receptor protein. Because this interaction depends on complementary 3D shapes and chemical charges, only target cells expressing the correct receptor will respond to a given ligand.
Where the receptor is located depends on the chemical properties of the ligand:
| Receptor Location | Ligand Properties | Examples of Ligands | Mechanism of Action |
|---|---|---|---|
| Plasma membrane (Cell-surface) | Large, polar, or charged (hydrophilic); cannot cross the hydrophobic lipid bilayer | Peptide hormones (e.g., insulin), growth factors, most neurotransmitters | Ligand binds extracellular domain conformational change in intracellular domain |
| Intracellular (Cytoplasm or Nucleus) | Small and nonpolar (hydrophobic); easily diffuses across the plasma membrane | Steroid hormones (e.g., estrogen, testosterone), thyroid hormone, nitric oxide | Ligand crosses membrane, binds receptor inside cell ligand-receptor complex often acts directly as a transcription factor |
2. Conformational change and membrane receptors
When a hydrophilic ligand binds to the extracellular ligand-binding domain of a plasma membrane receptor, the ligand does not enter the cell. Instead, binding induces a conformational change (shape change) in the receptor’s intracellular domain. This shape change initiates transduction by activating the intracellular domain’s enzymatic activity or exposing a binding site for intracellular relay proteins.
Two major membrane receptor classes appear frequently on the exam:
- G protein-coupled receptors (GPCRs): When a ligand binds the extracellular domain of a GPCR, its intracellular domain changes shape and activates an associated G protein by causing it to release GDP and bind GTP. The activated G protein then dissociates and binds to a nearby membrane enzyme (such as adenylyl cyclase), altering its activity.
- Ligand-gated ion channels: These transmembrane proteins act as gates. When a ligand (such as the neurotransmitter acetylcholine) binds to the receptor’s binding site, the channel protein undergoes a conformational change that opens (or closes) a central pore, allowing specific ions (such as , , or ) to diffuse rapidly across the membrane down their electrochemical gradients.