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Work at the C. S. M. laboratory is supported by the Spanish Agencia Estatal de Investigacion and European Regional Development Fund (BFU2016-74868-P and PID2019-104098 GB-I00/AEI/10.13039/501100011033); the Ministerio de Economia y Competitividad of Spain (BFU2013-41249-P and BIO2015-68990-REDT); and the Agencia Estatal CSIC (2019AEP045). The CNB-CSIC is further supported by a Severo Ochoa Excellence grant (SEV 2017-0712). M. L.-C. was a recipient of a Youth Employment Initiative contract co-funded by the European Social Fund and Regional Madrid Government (PEJ16/MED/TL-0935). P. J.d.P. acknowledges support by grants from the Spanish Ministry of Economy, Industry and Competitiveness projects (FIS2017-89549-R; "Maria de Maeztu" Program for Units of Excellence in R&D MDM2014-0377; and FIS2017-90701-REDT) and the Human Frontiers Science Program (HFSPO RGP0012/2018). R.D.-B. acknowledges funding from Spanish Ministry of Econonomy, Industry and Competitiveness FIS201786007-C3-1-P and the IFIMAC local project R&D MDM-2014-0377. A. V., P. J.d. P., and R. D. B. designed the research; M. L.-C. conducted specimen production; N. M.-G., A. O.-E., A. V., and P. J. d. P. conducted AFM experiments; A. V., P. I. F., and R. D. B. conducted theoretical analysis; C. S. M. supervised specimen production; R. D. B, A. V., and P. J. d. P. wrote the paper, with input from all other authors.

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Long-Range Cooperative Disassembly and Aging During Adenovirus Uncoating

Publicado en:Physical Review X. 11 (2): 021025- - 2021-04-30 11(2), DOI: 10.1103/PhysRevX.11.021025

Autores: Martin-Gonzalez, Natalia; Ibanez-Freire, Pablo; Ortega-Esteban, Alvaro; Laguna-Castro, Mara; San Martin, Carmen; Valbuena, Alejandro; Delgado-Buscalioni, Rafael; de Pablo, Pedro J

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Icosahedral virus capsids are closed shells built up with a hexagonal lattice of proteins, which incorporate pentamers at their fivefold vertices. Human adenovirus particles lose pentamers (pentons) during infection under a variety of physicochemical cues, including mechanical pulling of molecular motors and the viscous drag of the cytoplasm. By combining atomic force microscopy experiments with survival analysis and Markovian transition state theory, we investigate the sequence of adenovirus penton disassembly that reveals the aging of the virus structure. We show evidence that the lifetime of pentons gradually decreases, accompanied by capsid softening as neighboring pentons are lost. This cooperative dismantling process, which involves first-neighbor penton-penton distances of at least 45 nm, leads to a 50% increase in the virus disassembling rate of the virus particle. Theory and experiments fit remarkably well, allowing us to obtain the spontaneous escape rate and the energy barrier of penton disassembly (similar to 30 k(B)T). The observed increase in the penton's loss rate reveals long-range structural correlations within the capsid. Our estimations suggest that the mechanical cues arising from the strokes of protein motors carrying the virus to the nucleus could help penton disassembly and warrant the timely delivery of weak-enough capsids for adenovirus infection.

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