Reception: Ligands and Receptors

A receptor only responds to molecules that fit its binding site, the way a lock only turns for one key. That binding site is built from a specific arrangement of amino acids folded into a specific 3D shape. A ligand with the matching shape and chemistry fits snugly and forms weak bonds with the site; molecules of the wrong shape or charge simply don't stick. This specificity is why one hormone circulating through your whole bloodstream only affects the cells that carry its matching receptor.

Where the receptor sits depends on whether the ligand can cross the plasma membrane. The membrane is built from a phospholipid bilayer with a hydrophobic core, so only small, nonpolar molecules can slip through it directly. Steroid hormones, like estrogen and testosterone, are lipid-soluble, so they diffuse straight across the membrane and bind receptors floating in the cytoplasm or nucleus. Peptide hormones, like insulin, are chains of amino acids, polar and often too large to cross, so they must bind a receptor embedded in the plasma membrane itself, with its binding site facing outward.

Binding itself does nothing by itself; it only works because it forces the receptor to change shape. On a membrane receptor, that shape change on the outside flexes the whole protein, altering the part that faces the cytoplasm so it can now activate other molecules inside the cell. This is where reception hands off to transduction: the altered receptor starts a relay of internal signals, often a phosphorylation cascade, that carries the message onward until the cell actually responds, by dividing, secreting something, or changing its metabolism.