Chaperonin function depends on structure and disorder in co-chaperonin mobile loops.
Co-chaperonins from diverse organisms exhibit mobile loops which fold into a beta hairpin conformation upon binding to the chaperonin. GroES, Gp31, and human Hsp10 mobile loops exhibit a preference for the beta hairpin conformation in the free co-chaperonins, and the conformational dynamics of the human Hsp10 mobile loop appear to be restricted by nascent hairpin formation. Backbone conformational entropy must weigh against binding of co-chaperonins to chaperonins, and thus the conformational preferences of the loops may strongly influence chaperonin-binding affinity. Indeed, subtle mutations in the loops change GroEL-binding affinity and cause defects in chaperonin function, and these defects can be suppressed by mutations in GroEL which compensate for the changes in affinity. The fact that high-affinity co-chaperonin binding impairs chaperonin function has implications for the mechanism of chaperonin-assisted protein folding.
Landry
S J
SJ
Department of Biochemistry, Tulane University School of Medicine, New Orleans, LA 70112-2699, USA.
Steede
N K
NK
Garaudy
A M
AM
Maskos
K
K
Viitanen
P V
PV
D000595:Amino Acid Sequence; D018835:Chaperonin 10 / Q000737:chemistry / Q000378:metabolism; D018834:Chaperonin 60 / Q000737:chemistry / Q000378:metabolism; D018833:Chaperonins / Q000737:chemistry* / Q000378:metabolism*; D002950:Citrate (si)-Synthase / Q000737:chemistry / Q000378:metabolism; D003196:Computer Graphics; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009166:Mycobacterium leprae / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D018835:Chaperonin 10; D018834:Chaperonin 60; D002950:Citrate (si)-Synthase; D018833:Chaperonins