Kinetic intermediates trapped by native interactions in RNA folding.
In the magnesium ion-dependent folding of the Tetrahymena ribozyme, a kinetic intermediate accumulates in which the P4-P6 domain is formed, but the P3-P7 domain is not. The kinetic barriers to P3-P7 formation were investigated with the use of in vitro selection to identify mutant RNA molecules in which the folding rate of the P3-P7 domain was increased. The critical mutations disrupt native tertiary interactions within the P4-P6 domain and increase the rate of P3-P7 formation by destabilizing a kinetically trapped intermediate. Hence, kinetic traps stabilized by native interactions, and not simply by mispaired nonnative structures, can present a substantial barrier to RNA folding.
Treiber
D K
DK
Department of Molecular Biology, MB33, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Rook
M S
MS
Zarrinkar
P P
PP
Williamson
J R
JR
D000818:Animals; D001665:Binding Sites; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D009690:Nucleic Acid Conformation; D016337:RNA, Catalytic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013768:Tetrahymena / Q000737:chemistry
D016337:RNA, Catalytic; D008274:Magnesium