The Cleaved N-Terminus of pVI Binds Peripentonal Hexons in Mature Adenovirus

JOURNAL OF MOLECULAR BIOLOGY

卷:426

Article

Snijder, Joost^1,2,3  Benevento, Marco^1,2,3  Moyer, Crystal L.⁴  Reddy, Vijay⁵  Nemerow, Glen R.⁴  Heck, Albert J. R.^1,2,3 

[1] Univ Utrecht, Bijvoet Ctr Biomol Res, NL-3584 CH Utrecht, Netherlands

[2] Univ Utrecht, Utrecht Inst Pharmaceut Sci, NL-3584 CH Utrecht, Netherlands

[3] Netherlands Prote Ctr, NL-3584 CH Utrecht, Netherlands

[4] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA

[5] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA

关键词: virus maturation;    mass spectrometry;    native MS;    hydrogen-deuterium exchange;    adenovirus proteinase;   

DOI  :  10.1016/j.jmb.2014.02.022

来源: Elsevier

【 摘 要 】

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, pVln, 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. (c) 2014 Elsevier Ltd. All rights reserved.

【 授权许可】

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