分子伴侣和蛋白折叠

Most proteins cannot fold spontaneously into their native conformation as they are synthesized. Chaperones recognize exposed hydrophobic patches on unfolded proteins that would otherwise bind to other protein molecules, causing irreversible aggregation. By stabilizing unfolded or partially folded polypeptides, chaperones prevent misfolding and aggregation, allowing proteins to reach their correct three-dimensional structure.

The two major families of molecular chaperones are heat shock proteins hsp70 and hsp60. Hsp70 often acts while the protein is still being synthesized on the ribosome, recognizing hydrophobic amino acid stretches and trapping unfolded proteins. Hsp60, also called chaperonins, are large barrel-shaped complexes that provide an isolated chamber where proteins can fold in a protected environment away from other cellular proteins.

The hsp70 machinery recognizes small stretches of hydrophobic amino acids on a protein's surface while it remains attached to the ribosome. Hsp40 proteins trigger ATP hydrolysis, causing hsp70 to clamp around the unfolded protein like jaws. When ATP rebinds, hsp70 releases the polypeptide, allowing it to attempt folding. If folding fails, the cycle repeats until the protein achieves its native conformation.

A misfolded protein enters the chaperonin barrel through hydrophobic interactions at the opening, which often helps unfold the protein further. ATP binding seals the chamber with a cap, creating an isolated environment lined with hydrophilic surfaces. The protein folds in this protected space away from other cellular proteins. ATP hydrolysis and additional ATP binding eventually eject the cap and release the substrate protein.

Chaperones play a critical role in assembling complex proteins comprising multiple polypeptide chains. Each subunit must be correctly folded individually, then assembled in a specific manner. Chaperones stabilize unassociated components while other parts of the protein undergo assembly, ensuring proper folding and correct spatial arrangement of all subunits in the final protein complex.

Yes, chaperones stabilize partially unfolded polypeptides during transport across subcellular membranes, such as during mitochondrial protein import from the cytosol. Partially unfolded conformations are easier to transport across membranes than fully folded proteins. Chaperones maintain these unfolded states during transit, then facilitate proper refolding once the protein reaches its destination organelle.

Yes, the native conformation of a protein is determined solely by its amino acid sequence through interactions between side chains of constituent amino acids. Chaperones do not provide additional folding information; they catalyze the folding process without becoming part of the final protein. The amino acid sequence contains all the information needed for correct folding, and chaperones simply stabilize intermediates to prevent misfolding or aggregation.