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

Joost Snijder, Marco Benevento, Crystal L. Moyer, Vijay Reddy, Glen R. Nemerow, Albert J.R. Heck

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1971-1979
Number of pages9
JournalJournal of Molecular Biology
Volume426
Issue number9
DOIs
StatePublished - May 1 2014
Externally publishedYes

Bibliographical note

Funding Information:
We thank Tina-Marie Mullen for technical assistance. These studies were supported in part by National Institutes of Health grants HL054352 to G.R.N. and 5T32AI007354 to C.L.M. J.S., M.B. and A.J.R.H. are supported by the Netherlands Proteomics Centre and by the European Community's Seventh Framework Programme (FP7/2007–2013) by the PRIME-XS project grant agreement number 262067.

Keywords

  • adenovirus proteinase
  • hydrogen-deuterium exchange
  • mass spectrometry
  • native MS
  • virus maturation

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