tertiary structure

Take a single polypeptide chain — already dotted with helices and sheets — and let it collapse and pack into one compact, specific three-dimensional shape. That overall folded shape of the whole chain is its tertiary structure. If primary structure is the spelling and secondary structure is the words, tertiary structure is the finished sentence with a meaning: the working form of the protein.

What drives the chain into that one shape? The biggest force, surprisingly, comes from water. The greasy, nonpolar side chains cannot bond with water, so the chain folds to tuck them into a dry core, away from the surrounding water, while the water-loving side chains face outward — this is the hydrophobic effect, and it is the main engine of folding. Once that overall shape is set, it is reinforced by a handful of more specific contacts: hydrogen bonds, salt bridges between oppositely charged side chains, tight van der Waals packing where shapes fit snugly, and, in some proteins, covalent disulfide bonds that act like tacks holding two distant parts together. The fold is a balance of all these weak interactions; it is stable, but only marginally so, which is why heat or harsh chemicals can unfold (denature) a protein.

Tertiary structure is where function is born. The precise three-dimensional arrangement creates the pocket of an enzyme's active site, the binding cleft of a receptor, the channel of a transporter. Crucially, residues that are far apart in the sequence can be brought right next to each other in space by folding — an active site is often built from amino acids scattered all along the chain, only assembled into a working tool once the protein folds. This is why shape, not mere sequence, is what does the job.