The crystal structure of the asymmetric GroEL-GroES-(ADP)7 chaperonin complex.
Chaperonins assist protein folding with the consumption of ATP. They exist as multi-subunit protein assemblies comprising rings of subunits stacked back to back. In Escherichia coli, asymmetric intermediates of GroEL are formed with the co-chaperonin GroES and nucleotides bound only to one of the seven-subunit rings (the cis ring) and not to the opposing ring (the trans ring). The structure of the GroEL-GroES-(ADP)7 complex reveals how large en bloc movements of the cis ring's intermediate and apical domains enable bound GroES to stabilize a folding chamber with ADP confined to the cis ring. Elevation and twist of the apical domains double the volume of the central cavity and bury hydrophobic peptide-binding residues in the interface with GroES, as well as between GroEL subunits, leaving a hydrophilic cavity lining that is conducive to protein folding. An inward tilt of the cis equatorial domain causes an outward tilt in the trans ring that opposes the binding of a second GroES. When combined with new functional results, this negative allosteric mechanism suggests a model for an ATP-driven folding cycle that requires a double toroid.
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Z
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The Howard Hughes Medical Institute, The Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06510, USA.
Horwich
A L
AL
Sigler
P B
PB
D000244:Adenosine Diphosphate / Q000737:chemistry*; D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D001665:Binding Sites; D018835:Chaperonin 10 / Q000737:chemistry* / Q000235:genetics; D018834:Chaperonin 60 / Q000737:chemistry* / Q000235:genetics; D018360:Crystallography, X-Ray; D004926:Escherichia coli; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics
D018835:Chaperonin 10; D018834:Chaperonin 60; D046911:Macromolecular Substances; D011994:Recombinant Proteins; D000244:Adenosine Diphosphate