Protein-RNA complexation driven by the charge regulation mechanism

Biochem Biophys Res Commun. 2018 Mar 29;498(2):264-273. doi: 10.1016/j.bbrc.2017.07.027. Epub 2017 Jul 12.

Abstract

Electrostatic interactions play a pivotal role in many (bio)molecular association processes. The molecular organization and function in biological systems are largely determined by these interactions from pure Coulombic contributions to more peculiar mesoscopic forces due to ion-ion correlation and proton fluctuations. The latter is a general electrostatic mechanism that gives attraction particularly at low electrolyte concentrations. This charge regulation mechanism due to titrating amino acid and nucleotides residues is discussed here in a purely electrostatic framework. By means of constant-pH Monte Carlo simulations based on a fast coarse-grained titration proton scheme, a new computer molecular model was devised to study protein-RNA interactions. The complexation between the RNA silencing suppressor p19 viral protein and the 19-bp small interfering RNA was investigated at different solution pH and salt conditions. The outcomes illustrate the importance of the charge regulation mechanism that enhances the association between these macromolecules in a similar way as observed for other protein-polyelectrolyte systems typically found in colloidal science. Due to the highly negative charge of RNA, the effect is more pronounced in this system as predicted by the Kirkwood-Shumaker theory. Our results contribute to the general physico-chemical understanding of macromolecular complexation and shed light on the extensive role of RNA in the cell's life.

Keywords: Charge regulation; Electrostatics interactions; Monte carlo simulations; Protein titration; RNA titration; pH effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Hydrogen-Ion Concentration
  • Macromolecular Substances / chemistry*
  • Macromolecular Substances / metabolism
  • Models, Molecular
  • Monte Carlo Method
  • RNA, Small Interfering / chemistry*
  • RNA, Small Interfering / metabolism
  • Static Electricity
  • Viral Proteins / chemistry*
  • Viral Proteins / metabolism

Substances

  • Macromolecular Substances
  • RNA, Small Interfering
  • Viral Proteins