Chapter 15
Cooperativity and Allostery in RNA Systems
Alla Peselis and Alexander Serganov
Abstract
Allostery is among the most basic biological principles employed by biological macromolecules to achieve a
biologically active state in response to chemical cues. Although initially used to describe the impact of small
molecules on the conformation and activity of protein enzymes, the definition of this term has been
significantly broadened to describe long-range conformational change of macromolecules in response to
small or large effectors. Such a broad definition could be applied to RNA molecules, which do not typically
serve as protein-free cellular enzymes but fold and form macromolecular assemblies with the help of various
ligand molecules, including ions and proteins. Ligand-induced allosteric changes in RNA molecules are
often accompanied by cooperative interactions between RNA and its ligand, thus streamlining the folding
and assembly pathways. This chapter provides an overview of the interplay between cooperativity and
allostery in RNA systems and outlines methods to study these two biological principles.
Key words RNA cooperativity, Thermodynamics, Conformational change
1 Introduction
The vast majority of functional macromolecules are a result of
primary sequences properly folded into secondary, tertiary, and
quaternary structures. In order to achieve functional conformations, biopolymers such as proteins and nucleic acids must proceed
through a folding pathway(s), which could initially yield a large
pool of partially folded conformations and nonfunctional states.
Often times, in order to adopt the active state, macromolecules
have to sample a broad number of possible states and finalize their
conformation by making a proper set of intermolecular interactions
or binding to specific ligands [1]. Interactions with ligands can
depend on their presence in the cells and environment, and, therefore, can impose a regulatory effect on the function of a macromolecule. A structural change of a molecule in response to ligand
binding has been defined as an allosteric modulation.
Like proteins, some RNA needs to fold into three-dimensional
structures and undergo structural transitions to carry out biological
function [2]. RNA does not have many functional groups and is,
Luisa Di Paola and Alessandro Giuliani (eds.), Allostery: Methods and Protocols, Methods in Molecular Biology, vol. 2253,
https://doi.org/10.1007/978-1-0716-1154-8_15, © Springer Science+Business Media, LLC, part of Springer Nature 2021
255
Cooperativity and Allostery in RNA Systems
Alla Peselis and Alexander Serganov
Abstract
Allostery is among the most basic biological principles employed by biological macromolecules to achieve a
biologically active state in response to chemical cues. Although initially used to describe the impact of small
molecules on the conformation and activity of protein enzymes, the definition of this term has been
significantly broadened to describe long-range conformational change of macromolecules in response to
small or large effectors. Such a broad definition could be applied to RNA molecules, which do not typically
serve as protein-free cellular enzymes but fold and form macromolecular assemblies with the help of various
ligand molecules, including ions and proteins. Ligand-induced allosteric changes in RNA molecules are
often accompanied by cooperative interactions between RNA and its ligand, thus streamlining the folding
and assembly pathways. This chapter provides an overview of the interplay between cooperativity and
allostery in RNA systems and outlines methods to study these two biological principles.
Key words RNA cooperativity, Thermodynamics, Conformational change
1 Introduction
The vast majority of functional macromolecules are a result of
primary sequences properly folded into secondary, tertiary, and
quaternary structures. In order to achieve functional conformations, biopolymers such as proteins and nucleic acids must proceed
through a folding pathway(s), which could initially yield a large
pool of partially folded conformations and nonfunctional states.
Often times, in order to adopt the active state, macromolecules
have to sample a broad number of possible states and finalize their
conformation by making a proper set of intermolecular interactions
or binding to specific ligands [1]. Interactions with ligands can
depend on their presence in the cells and environment, and, therefore, can impose a regulatory effect on the function of a macromolecule. A structural change of a molecule in response to ligand
binding has been defined as an allosteric modulation.
Like proteins, some RNA needs to fold into three-dimensional
structures and undergo structural transitions to carry out biological
function [2]. RNA does not have many functional groups and is,
Luisa Di Paola and Alessandro Giuliani (eds.), Allostery: Methods and Protocols, Methods in Molecular Biology, vol. 2253,
https://doi.org/10.1007/978-1-0716-1154-8_15, © Springer Science+Business Media, LLC, part of Springer Nature 2021
255