Cells coordinate behaviour by sending chemical messages. In signal transduction, the critical first step is the ligand–receptor interaction, where the chemistry of the ligand determines which cells respond and how strongly.

Core idea: ligands start signalling by binding receptors

A ligand released from a signalling cell acts as a chemical “word” in a molecular language. Only cells with the matching receptor can “read” that word, making communication highly selective.

Ligand binding depends on complementarity: the ligand’s shape and chemical properties match a binding site on the receptor protein. If a cell lacks the receptor, it is not a target and typically shows no direct response to that ligand.

What ligands do (and do not do)

Ligands are best understood as information-carrying molecules rather than sources of energy or building blocks. Their main roles are to:

• Convey specificity: the ligand identifies which receptor should be engaged.

• Control timing: signals can be rapid (released and degraded quickly) or sustained (released continuously).

• Set response strength: response often depends on how much ligand is available and how long receptors remain occupied.

Ligands do not automatically cause a response just by being present; binding to a complementary receptor protein is the initiating event that allows intracellular signalling to begin.

Chemical variety of ligands emphasised in AP Biology

The syllabus highlights that ligands can be peptides or small molecules. These categories matter because chemical properties influence how ligands move and how they are handled outside cells.

Peptide (protein) ligands

Peptide ligands are chains of amino acids released from cells. Key functional implications:

• Typically water-soluble, so they can disperse in extracellular fluid.

• Often short-lived due to breakdown by extracellular enzymes, enabling tight control.

• Commonly used when organisms need precise, rapidly adjustable signalling.

Small-molecule ligands

Small molecules include many structurally diverse chemicals (for example, modified amino acids, nucleotides, or lipids). Key functional implications:

• Their small size can support fast diffusion over short distances.

• Some are readily modified or inactivated by enzymes, which can terminate signalling quickly.

• Different small molecules can carry distinct “meanings” even at very low concentrations because receptors can be highly discriminating.

Receptor complementarity and specificity

A receptor protein has a binding site that interacts with a ligand through noncovalent forces (such as hydrogen bonds, ionic interactions, and hydrophobic effects). Specificity arises because:

• The receptor’s binding site has a unique three-dimensional arrangement.

• Only ligands with the right functional groups and geometry bind effectively.

• Binding can trigger a receptor conformational change (a shape shift) that initiates signalling inside the cell.

This diagram summarizes the basic architecture of a G protein–coupled receptor (GPCR), a common class of cell-surface receptors with seven membrane-spanning helices. The labeled extracellular loops help illustrate where ligand recognition can occur, while the intracellular loops connect receptor activation to downstream signaling proteins. Viewing the receptor as a transmembrane “switch” helps explain why ligand binding can initiate signaling inside the cell. Source

Because ligand–receptor binding is selective, different cell types in the same environment can respond differently to the same ligand depending on which receptors they express.

Signal strength: concentration, affinity, and saturation

Even without changing receptor type, cells can tune responsiveness based on binding dynamics:

• Ligand concentration: higher ligand levels generally increase receptor occupancy, up to a limit.

• Affinity: receptors differ in how tightly they bind a ligand; higher affinity means effective binding at lower ligand concentrations.

• Saturation: once most receptors are occupied, adding more ligand produces little additional increase in initial binding.

This graph shows how receptor occupancy increases with ligand concentration and then plateaus as receptors become saturated (approaching Bmax). The midpoint of the curve corresponds to $K_D$, the ligand concentration that produces 50% receptor occupancy, linking affinity to how much ligand is needed for binding. The semilog x-axis emphasizes how occupancy changes across orders of magnitude in ligand concentration. Source

These features help explain why very low ligand amounts can still be biologically meaningful, and why responses often show thresholds and plateaus.

This simple binding curve plots fractional receptor occupancy (y) against ligand concentration (L), showing the characteristic rise and saturation expected for one-site binding. The arrow marks $K_D$ at y = 0.5, emphasizing that affinity can be read from the ligand concentration needed for half-saturation. The asymptotic approach to y = 1 highlights why adding ligand eventually produces diminishing increases in binding. Source

How ligands reach target cells

Ligands must encounter receptors to initiate signalling. Common features of ligand delivery include:

• Release from a signalling cell into extracellular space (or presentation at the cell surface).

• Movement through diffusion in extracellular fluid; in some contexts, movement can be guided by binding to extracellular components that localise the signal.

• Removal by degradation, uptake, or diffusion away, which limits signalling duration and prevents inappropriate activation.

Common ligand vocabulary: agonists and antagonists

Ligands can differ in their effect on receptor activity:

• Agonist ligands bind and promote receptor activation.

• Antagonist ligands bind but reduce or block receptor activation by preventing the normal ligand from binding.

This distinction reinforces that ligand binding is the gatekeeping step in signalling: who binds the receptor, and how, determines whether signalling begins.