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J Mol Biol. 2014 May 1;426(9):1971-9. doi: 10.1016/j.jmb.2014.02.022. Epub 2014 Mar 5.

The cleaved N-terminus of pVI binds peripentonal hexons in mature adenovirus.

Author information

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; Netherlands Proteomics Centre, Padualaan 8, 3584 CH Utrecht, The Netherlands.
2
Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
3
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
4
Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: gnemerow@scripps.edu.
5
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; Netherlands Proteomics Centre, Padualaan 8, 3584 CH Utrecht, The Netherlands. Electronic address: a.j.r.heck@uu.nl.

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.

KEYWORDS:

adenovirus proteinase; hydrogen–deuterium exchange; mass spectrometry; native MS; virus maturation

PMID:
24613303
PMCID:
PMC4057896
DOI:
10.1016/j.jmb.2014.02.022
[Indexed for MEDLINE]
Free PMC Article

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