Uncovering metastability and disassembly hotspots in whole viral particles

Publication date: Available online 13 December 2018Source: Progress in Biophysics and Molecular BiologyAuthor(s): Ranita Ramesh, Xin Xiang Lim, Palur Venkata Raghuvamsi, Wu Chao, Wong Sek Man, Ganesh Srinivasan AnandAbstractViruses are metastable macromolecular assemblies that toggle between multiple conformational states through molecular rearrangements that are critical for mediating viral host entry. Viruses respond to different host specific environmental cues to form disassembly intermediates for the eventual release of genomic material required for replication. Although static snapshots of these intermediates have been captured through structural techniques such as X-ray crystallography and cryo-EM, the mechanistic details of these conformational rearrangements underpinning viral metastability have been poorly understood. Amide hydrogen deuterium exchange mass spectrometry (HDXMS) is a powerful tool that measures hydrogen bonding propensities to probe changes in the dynamics of different macromolecular interactions. Chaotropic agents such as urea can be used to disrupt hydrogen bonds between different subunits, thereby ranking regions of the virus that are critical in maintaining viral stability. By controlled urea denaturation with HDXMS, we have identified specific loci in a Turnip Crinkle Virus (TCV) model showing increased deuterium exchange with even minimally disruptive concentrations of urea. These loci represent dynamic disassembly hotspots. These hotspots are p...
Source: Progress in Biophysics and Molecular Biology - Category: Molecular Biology Source Type: research