Interaction of 4,4'-dithiodipyridine with Cys(458) triggers disassembly of GroEL.
Chaperonin GroEL, consisting of two seven-subunit rings stacked back-to-back, is disassembled by interaction of 4, 4'-dithiodipyridine (DTP) with Cys(458) located close to the intersubunit contacts within and between the rings. The thiol group of Cys(458) is inaccessible to the probe being buried into the pocket locked by segment Asn(475)-Asn(487). Flexibility of this segment is proposed to induce the "open" state of the pocket and accommodate the bulky probe inside so that the consequential irreversible shifts in the pocket constituents disassemble GroEL. This scheme is supported by the finding that DTP-induced disassembly of GroEL is facilitated by ATP, which specifically stimulates a local shift of the segment Asn(475)-Asn(487) into solution.
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
E
E
Bochkareva
M
M
Safro
A
A
Girshovich
D018834:Chaperonin 60 / Q000737:chemistry* / Q000378:metabolism; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D004220:Disulfides / Q000378:metabolism*; D011487:Protein Conformation; D011725:Pyridines / Q000378:metabolism*; D013439:Sulfhydryl Reagents / Q000378:metabolism
D018834:Chaperonin 60; D004220:Disulfides; D011725:Pyridines; D013439:Sulfhydryl Reagents; C007542:4,4'-dipyridyl disulfide; D003545:Cysteine