An essential cellular machinery that has been identified and studied only relatively recently is a collective of specialized proteins, molecular chaperones, that bind nonnative states of other proteins and assist them to reach a functional conformation, in most cases through the expenditure of ATP. Originally identified by their increased abundance following heat shock, chaperone proteins in general recognize exposed hydrophobic surfaces of nonnative species, surfaces that will ultimately be buried in the native state, and form noncovalent interactions with them, stabilizing them against irreversible multimeric aggregation. Release of polypeptide then follows, in many cases driven by an ATP-directed conformational change of the chaperone, permitting subsequent steps of polypeptide folding or biogenesis to occur. When such steps fail to proceed productively, recognition and rebinding by the same or another chaperone can occur, allowing another opportunity for a productive conformation to be reached.

Different classes of molecular chaperones appear to be directed to binding specific nonnative states, the nature of which are beginning to be understood. For example, the two best-studied families, examined in detail below, the ubiquitous Hsp70 and Hsp60 (chaperonin) chaperones, recognize hydrophobic surface in the context of, respectively, extended and collapsed (globular) conformations, which are bound correspondingly either by local enclosure of the chain or by global enclosure of the polypeptide in a central cavity. Because there is not yet the detailed level of structural and mechanistic understanding for other recognized families of chaperones, they are not considered here, but important observations concerning binding, nucleotide use, and cellular actions are summarized in Table 1.