The role of molecular chaperones in protein folding.
Folding of newly synthesized polypeptides in the crowded cellular environment requires the assistance of so-called molecular chaperone proteins. Chaperones of the Hsp70 class and their partner proteins interact with nascent polypeptide chains on ribosomes and prevent their premature (mis)folding at least until a domain capable of forming a stable structure is synthesized. For many proteins, completion of folding requires the subsequent interaction with one of the large oligomeric ring-shaped proteins of the chaperonin family, which is composed of the GroEL-like proteins in eubacteria, mitochondria, and chloroplasts, and the TRiC family in eukaryotic cytosol and archaea. These proteins bind partially folded polypeptide in their central cavity and promote folding by ATP-dependent cycles of release and rebinding. In these reactions, molecular chaperones interact predominantly with the hydrophobic surfaces exposed by nonnative polypeptides, thereby preventing incorrect folding and aggregation.
Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
J P
JP
Hendrick
F U
FU
Hartl
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D018834:Chaperonin 60 / Q000502:physiology; D005057:Eukaryotic Cells / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000145:classification / Q000502:physiology; D018832:Molecular Chaperones / Q000502:physiology*; D011387:Prokaryotic Cells / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis; D011487:Protein Conformation; D017510:Protein Folding; D013329:Structure-Activity Relationship
D018834:Chaperonin 60; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones