Structural features of the GroEL-GroES nano-cage required for rapid folding of encapsulated protein.
GroEL and GroES form a chaperonin nano-cage for proteins up to approximately 60 kDa to fold in isolation. Here we explored the structural features of the chaperonin cage critical for rapid folding of encapsulated substrates. Modulating the volume of the GroEL central cavity affected folding speed in accordance with confinement theory. Small proteins (approximately 30 kDa) folded more rapidly as the size of the cage was gradually reduced to a point where restriction in space slowed folding dramatically. For larger proteins (approximately 40-50 kDa), either expanding or reducing cage volume decelerated folding. Additionally, interactions with the C-terminal, mildly hydrophobic Gly-Gly-Met repeat sequences of GroEL protruding into the cavity, and repulsion effects from the negatively charged cavity wall were required for rapid folding of some proteins. We suggest that by combining these features, the chaperonin cage provides a physical environment optimized to catalyze the structural annealing of proteins with kinetically complex folding pathways.
Tang
Yun-Chi
YC
Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany.
Chang
Hung-Chun
HC
Roeben
Annette
A
Wischnewski
Dirk
D
Wischnewski
Nadine
N
Kerner
Michael J
MJ
Hartl
F Ulrich
FU
Hayer-Hartl
Manajit
M
D000595:Amino Acid Sequence / Q000502:physiology; D001426:Bacterial Proteins / Q000378:metabolism*; D018835:Chaperonin 10 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018834:Chaperonin 60 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism; D008958:Models, Molecular; D008970:Molecular Weight; D009154:Mutation / Q000502:physiology; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary / Q000502:physiology
D001426:Bacterial Proteins; D018835:Chaperonin 10; D018834:Chaperonin 60