Collision induced unfolding and molecular dynamics simulations of norovirus capsid dimers reveal strain-specific stability profiles

Collision induced unfolding (CIU) is a method used with ion mobility mass spectrometry to examine protein structures and their stability. Such experiments yield information about higher order protein structures, yet are unable to provide details about the underlying processes. That information can h...

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Bibliographic Details
Published in:Physical chemistry chemical physics : PCCP 2024-05, Vol.26 (17), p.1394-1315
Main Authors: Brodmerkel, Maxim N, Thiede, Lars, De Santis, Emiliano, Uetrecht, Charlotte, Caleman, Carl, Marklund, Erik G
Format: Article
Language:English
Subjects:
Capsid - chemistry
Capsid Proteins - chemistry
Capsid Proteins - metabolism
Dimers
Dynamic stability
Ionic mobility
Mass spectrometry
Molecular dynamics
Molecular Dynamics Simulation
Norovirus - chemistry
Protein Multimerization
Protein Stability
Protein Unfolding
Proteins
Simulation
Structural stability
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Summary:Collision induced unfolding (CIU) is a method used with ion mobility mass spectrometry to examine protein structures and their stability. Such experiments yield information about higher order protein structures, yet are unable to provide details about the underlying processes. That information can however be provided using molecular dynamics simulations. Here, we investigate the gas-phase unfolding of norovirus capsid dimers from the Norwalk and Kawasaki strains by employing molecular dynamics simulations over a range of temperatures, representing different levels of activation, together with CIU experiments. The dimers have highly similar structures, but their CIU reveals different stability that can be explained by the different dynamics that arises in response to the activation seen in the simulations, including a part of the sequence with previously observed strain-specific dynamics in solution. Our findings show how similar protein variants can be examined using mass spectrometric techniques in conjunction with atomistic molecular dynamics simulations to reveal differences in stability as well as differences in how and where unfolding takes place upon activation. Ion mobility mass spectrometry and molecular dynamics simulations reveal strain-dependent stability and unfolding in the VP1 dimer from the norovirus capsid.
ISSN:1463-9076
1463-9084
1463-9084
DOI:10.1039/d3cp06344e