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Virus Capsid Dissolution Studied by Microsecond Molecular Dynamics Simulations
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräknings- och systembiologi.
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Struktur- och molekylärbiologi.
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräknings- och systembiologi.
2012 (Engelska)Ingår i: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 8, nr 5, s. e1002502-Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Dissolution of many plant viruses is thought to start with swelling of the capsid caused by calcium removal following infection, but no high-resolution structures of swollen capsids exist. Here we have used microsecond all-atom molecular simulations to describe the dynamics of the capsid of satellite tobacco necrosis virus with and without the 92 structural calcium ions. The capsid expanded 2.5% upon removal of the calcium, in good agreement with experimental estimates. The water permeability of the native capsid was similar to that of a phospholipid membrane, but the permeability increased 10-fold after removing the calcium, predominantly between the 2-fold and 3-fold related subunits. The two calcium binding sites close to the icosahedral 3-fold symmetry axis were pivotal in the expansion and capsid-opening process, while the binding site on the 5-fold axis changed little structurally. These findings suggest that the dissociation of the capsid is initiated at the 3-fold axis.

Ort, förlag, år, upplaga, sidor
2012. Vol. 8, nr 5, s. e1002502-
Nationell ämneskategori
Biofysik Strukturbiologi
Identifikatorer
URN: urn:nbn:se:uu:diva-171701DOI: 10.1371/journal.pcbi.1002502ISI: 000305964600012OAI: oai:DiVA.org:uu-171701DiVA, id: diva2:512039
Tillgänglig från: 2012-03-26 Skapad: 2012-03-26 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
Ingår i avhandling
1. Exploring the Molecular Dynamics of Proteins and Viruses
Öppna denna publikation i ny flik eller fönster >>Exploring the Molecular Dynamics of Proteins and Viruses
2012 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Knowledge about structure and dynamics of the important biological macromolecules — proteins, nucleic acids, lipids and sugars — helps to understand their function. Atomic-resolution structures of macromolecules are routinely captured with X-ray crystallography and other techniques. In this thesis, simulations are used to explore the dynamics of the molecules beyond the static structures.

Viruses are machines constructed from macromolecules. Crystal structures of them reveal little to no information about their genomes. In simulations of empty capsids, we observed a correlation between the spatial distribution of chloride ions in the solution and the position of RNA in crystals of satellite tobacco necrosis virus (STNV) and satellite tobacco mosaic virus (STMV). In this manner, structural features of the non-symmetric RNA could also be inferred.

The capsid of STNV binds calcium ions on the icosahedral symmetry axes. The release of these ions controls the activation of the virus particle upon infection. Our simulations reproduced the swelling of the capsid upon removal of the ions and we quantified the water permeability of the capsid. The structure and dynamics of the expanded capsid suggest that the disassembly is initiated at the 3-fold symmetry axis.

Several experimental methods require biomolecular samples to be injected into vacuum, such as mass-spectrometry and diffractive imaging of single particles. It is therefore important to understand how proteins and molecule-complexes respond to being aerosolized. In simulations we mimicked the dehydration process upon going from solution into the gas phase. We find that two important factors for structural stability of proteins are the temperature and the level of residual hydration. The simulations support experimental claims that membrane proteins can be protected by a lipid micelle and that a non-membrane protein could be stabilized in a reverse micelle in the gas phase. A water-layer around virus particles would impede the signal in diffractive experiments, but our calculations estimate that it should be possible to determine the orientation of the particle in individual images, which is a prerequisite for three-dimensional reconstruction.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2012. s. 45
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 919
Nyckelord
molecular dynamics, virus dynamics, capsid dissolution, satellite tobacco necrosis virus, satellite tobacco mosaic virus, virus genome structure, gas phase protein structure, water layer, micelle embedded protein, membrane protein
Nationell ämneskategori
Biologiska vetenskaper Biokemi och molekylärbiologi Biofysik Strukturbiologi
Forskningsämne
Kemi med inriktning mot biofysik
Identifikatorer
urn:nbn:se:uu:diva-172284 (URN)978-91-554-8335-7 (ISBN)
Disputation
2012-05-25, B41, Uppsala Biomedicinska Centrum, Husargatan 3, Uppsala, 09:15 (Engelska)
Opponent
Handledare
Anmärkning
BMC B41, 25/5, 9:15Tillgänglig från: 2012-05-04 Skapad: 2012-04-03 Senast uppdaterad: 2012-08-01Bibliografiskt granskad

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