Adenovirus core protein V reinforces the capsid and enhances genome release from disrupted particles
EntityUAM. Departamento de Física de la Materia Condensada
PublisherAmerican Association for the Advancement of Science
10.1126/sciadv.ade9910Science Advances 9.14 (2023): eade9910
Funded byThis work was supported by grants from the Spanish Ministry of Economy, Industry and Competitiveness (FIS2017-89549-R; “Maria de Maeztu” Program for Units of Excellence in R&D MDM-2014-0377 and FIS2017-90701-REDT) and from the Human Frontiers Science Program (HFSPO RGP0012/2018) to P.J.d.P., as well as grant PID2019-104098GB-I00/AEI/10.13039/501100011033, cofunded by the Spanish State Research Agency and the European Regional Development Fund to C.S.M. The CNB-CSIC was further supported by a Spanish State Research Agency Severo Ochoa Excellence grant (SEV 2017-0712). C.S.M. is a member of the CSIC funded consortium LifeHub (CSIC grant number: 202120E47). M.H.-P. was a recipient of a Juan de la Cierva postdoctoral contract and currently holds a Ramón y Cajal position (RyC2021-030929-I) funded by the Spanish State Research Agency. M.H.-P. acknowledges funding from Ayudas a Proyectos de I+D para Jóvenes Doctores de la Universidad Autónoma de Madrid 2021, SI3/PJI/2021-00216 supported by the Community of Madrid and the University Autónoma de Madrid, and TED2021-129937B-I00 from Spanish Ministry of Science and Innovation. Financial support of the Community of Madrid and the European Union through the European Regional Development Fund (ERDF), financed as part of the Union response to Covid-19 pandemic (VIRMAT-REACT), is also acknowledged. Access to the cryo-EM CNB-CSIC facility was carried out via the CRIOMECORR project (ESFRI-2019-01- CSIC-16). Work in the Greber laboratory was supported by a grant to UFG from Schweizerischer Nationalfonds (Swiss National Science Foundation, 31003A_179256/1). Author contributions: N.M.-G. performed AFM experiments and analyzed the data. M.H.-P. and C.S.M. carried out cryoEM analyses. A.G.-G. and M.B. produced the viral samples and carried out thermostability analyses. U.F.G., C.S.M., and P.J.d.P. designed research. N.M.-G. wrote the manuscript, with input from U.F.G., C.S.M., and P.J.d.P. All authors read and edited the manuscript. Competing interests: The authors declare that they have no competing interests. Data and materials availability: The Ad5-ΔV cryo-EM map is deposited at the Electron Microscopy Data Bank (EMDB; www.ebi.ac.uk/pdbe/emdb) with accession number EMD-15694. All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials
ProjectGobierno de España. FIS2017-89549-R; Gobierno de España. MDM-2014-0377; Gobierno de España. FIS2017-90701-REDT; Gobierno de España. PID2019-104098GB-I00; Gobierno de España. SEV-2017-0712; Gobierno de España. TED2021-129937B-I00
SubjectsAdenovirus; Protein V; Ad5-ΔV; Física
Rights© 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.
Out of the three core proteins in human adenovirus, protein V is believed to connect the inner capsid surface to the outer genome layer. Here, we explored mechanical properties and in vitro disassembly of particles lacking protein V (Ad5-ΔV). Ad5-ΔV particles were softer and less brittle than the wild-type ones (Ad5-wt), but they were more prone to release pentons under mechanical fatigue. In Ad5-ΔV, core components did not readily diffuse out of partially disrupted capsids, and the core appeared more condensed than in Ad5-wt. These observations suggest that instead of condensing the genome, protein V antagonizes the condensing action of the other core proteins. Protein V provides mechanical reinforcement and facilitates genome release by keeping DNA connected to capsid fragments that detach during disruption. This scenario is in line with the location of protein V in the virion and its role in Ad5 cell entry
Google Scholar:Martín-González, Natalia - Gómez-González, Alfonso - Hernando-Pérez, Mercedes - Bauer, Michael - Greber, Urs F. - Martín, Carmen San - Pablo Gómez, Pedro José de
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