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GroEL‐GroES‐mediated protein folding
Author(s) -
Horwich Arthur,
Chapman Eli,
Koculi Eda,
Apetri Adrian,
Fenton Wayne A.,
Farr George,
Horst Reto,
Wüthrich Kurt
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.536.2
Subject(s) - groel , groes , chaperonin , folding (dsp implementation) , protein folding , biophysics , chemistry , crystallography , chaperone (clinical) , biochemistry , biology , medicine , escherichia coli , pathology , electrical engineering , gene , engineering
The chaperonin system assists the folding of a large variety of proteins by two actions: binding in the hydrophobic central cavity of an open ring and folding mediated in a subsequently GroES‐encapsulated hydrophilic chamber. We have been studying the GroEL system both in vivo and in vitro, and report on recent results. In one experiment in vitro, we have used hydrogen‐deuterium exchange and NMR spectroscopy to compare the folding trajectories of human DHFR while folding free in solution and inside a stable GroEL‐GroES complex formed by a single ring version of GroEL, SR1, and GroES. We observe that identical trajectories are taken, involving early formation of the central parallel beta‐sheet of DHFR followed by formation of flanking alpha helices. The recovery of native DHFR is only ~40% in the spontaneous reaction, however, where the remaining molecules are subject to aggregation, vs nearly 100% recovery of native DHFR in the GroEL‐GroES reaction. Thus the sequestered chaperonin cavity appears to forestall or, as evidenced by other experiments, can “correct” misfolded states to support productive folding.