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Title: Perturbation of the Hierarchical Folding of a Large RNA by the Destabilization of its Scaffold's Tertiary Structure

Abstract

The P4-P6 domain serves as a scaffold against which the periphery and catalytic core organize and fold during Mg{sup 2+}-mediated folding of the Tetrahymena thermophila ribozyme. The most prominent structural motif of the P4-P6 domain is the tetraloop-tetraloop receptor interaction which 'clamps' the distal parts of its hairpin-like structure. Destabilization of the tertiary structure of the P4-P6 domain by perturbation of the tetraloop-tetraloop receptor interaction alters the Mg{sup 2+}-mediated folding pathway. The folding hierarchy of P5c{approx}P4-P6>periphery>catalytic core that is a striking attribute of the folding of the wild-type RNA is abolished. The initial steps in folding of the mutant RNA are {ge}50-fold faster than those of the wild-type ribozyme with the earliest observed tertiary contacts forming around regions known to specifically bind Mg{sup 2+}. The interaction between the mutant tetraloop and the tetraloop receptor appears coincidently with slowly forming catalytic core tertiary contacts. Thus, the stability conferred upon the P4-P6 domain by the tetraloop-tetraloop receptor interaction dictates the preferred folding pathway by stabilizing an early intermediate. A sub-denaturing concentration of urea diminishes the early barrier to folding the wild-type ribozyme along with complex effects on the subsequent steps of folding the wild-type and mutant RNA.

Authors:
;
Publication Date:
Research Org.:
Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
913910
Report Number(s):
BNL-78478-2007-JA
Journal ID: ISSN 0022-2836; JMOBAK; TRN: US200804%%287
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Journal Name:
J. Mol. Biol.
Additional Journal Information:
Journal Volume: 354; Journal ID: ISSN 0022-2836
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; MUTANTS; RNA; STABILITY; TETRAHYMENA; UREA; national synchrotron light source

Citation Formats

Shcherbakova, I, and Brenowitz, M. Perturbation of the Hierarchical Folding of a Large RNA by the Destabilization of its Scaffold's Tertiary Structure. United States: N. p., 2005. Web. doi:10.1016/j.jmb.2005.09.032.
Shcherbakova, I, & Brenowitz, M. Perturbation of the Hierarchical Folding of a Large RNA by the Destabilization of its Scaffold's Tertiary Structure. United States. https://doi.org/10.1016/j.jmb.2005.09.032
Shcherbakova, I, and Brenowitz, M. 2005. "Perturbation of the Hierarchical Folding of a Large RNA by the Destabilization of its Scaffold's Tertiary Structure". United States. https://doi.org/10.1016/j.jmb.2005.09.032.
@article{osti_913910,
title = {Perturbation of the Hierarchical Folding of a Large RNA by the Destabilization of its Scaffold's Tertiary Structure},
author = {Shcherbakova, I and Brenowitz, M},
abstractNote = {The P4-P6 domain serves as a scaffold against which the periphery and catalytic core organize and fold during Mg{sup 2+}-mediated folding of the Tetrahymena thermophila ribozyme. The most prominent structural motif of the P4-P6 domain is the tetraloop-tetraloop receptor interaction which 'clamps' the distal parts of its hairpin-like structure. Destabilization of the tertiary structure of the P4-P6 domain by perturbation of the tetraloop-tetraloop receptor interaction alters the Mg{sup 2+}-mediated folding pathway. The folding hierarchy of P5c{approx}P4-P6>periphery>catalytic core that is a striking attribute of the folding of the wild-type RNA is abolished. The initial steps in folding of the mutant RNA are {ge}50-fold faster than those of the wild-type ribozyme with the earliest observed tertiary contacts forming around regions known to specifically bind Mg{sup 2+}. The interaction between the mutant tetraloop and the tetraloop receptor appears coincidently with slowly forming catalytic core tertiary contacts. Thus, the stability conferred upon the P4-P6 domain by the tetraloop-tetraloop receptor interaction dictates the preferred folding pathway by stabilizing an early intermediate. A sub-denaturing concentration of urea diminishes the early barrier to folding the wild-type ribozyme along with complex effects on the subsequent steps of folding the wild-type and mutant RNA.},
doi = {10.1016/j.jmb.2005.09.032},
url = {https://www.osti.gov/biblio/913910}, journal = {J. Mol. Biol.},
issn = {0022-2836},
number = ,
volume = 354,
place = {United States},
year = {Sat Jan 01 00:00:00 EST 2005},
month = {Sat Jan 01 00:00:00 EST 2005}
}