The Cleaved N-Terminus of pVI Binds Peripentonal Hexons in Mature Adenovirus |
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Authors: | Joost Snijder Marco Benevento Crystal L. Moyer Vijay Reddy Glen R. Nemerow Albert J.R. Heck |
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Affiliation: | 1 Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands;2 Netherlands Proteomics Centre, Padualaan 8, 3584 CH Utrecht, The Netherlands;3 Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA;4 Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA |
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Abstract: | Mature human adenovirus particles contain four minor capsid proteins, in addition to the three major capsid proteins (penton base, hexon and fiber) and several proteins associated with the genomic core of the virion. Of the minor capsid proteins, VI plays several crucial roles in the infection cycle of the virus, including hexon nuclear targeting during assembly, activation of the adenovirus proteinase (AVP) during maturation and endosome escape following cell entry. VI is translated as a precursor (pVI) that is cleaved at both N- and C-termini by AVP. Whereas the role of the C-terminal fragment of pVI, pVIc, is well established as an important co-factor of AVP, the role of the N-terminal fragment, pVIn, is currently elusive. In fact, the fate of pVIn following proteolytic cleavage is completely unknown. Here, we use a combination of proteomics-based peptide identification, native mass spectrometry and hydrogen–deuterium exchange mass spectrometry to show that pVIn is associated with mature human adenovirus, where it binds at the base of peripentonal hexons in a pH-dependent manner. Our findings suggest a possible role for pVIn in targeting pVI to hexons for proper assembly of the virion and timely release of the membrane lytic mature VI molecule. |
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Keywords: | AVP, adenovirus proteinase NLS, nuclear localization signal MS, mass spectrometry HDX, hydrogen&ndash deuterium exchange LC, liquid chromatography FA, formic acid HCD, higher energy collision dissociation ETD, electron transfer dissociation |
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