Structures and organization of adenovirus cement proteins provide insights into the role of capsid maturation in virus entry and infection

Vijay S. Reddy, Glen R. Nemerow

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

Adenovirus cement proteins play crucial roles in virion assembly, disassembly, cell entry, and infection. Based on a refined crystal structure of the adenovirus virion at 3.8-Å resolution, we have determined the structures of all of the cement proteins (IIIa, VI, VIII, and IX) and their organization in two distinct layers. We have significantly revised the recent cryoelectron microscopy models for proteins IIIa and IX and show that both are located on the capsid exterior. Together, the cement proteins exclusively stabilize the hexon shell, thus rendering penton vertices the weakest links of the adenovirus capsid. We describe, for the first time to our knowledge, the structure of protein VI, a key membrane-lytic molecule, and unveil its associations with VIII and core protein V, which together glue peripentonal hexons beneath the vertex region and connect them to the rest of the capsid on the interior. Following virion maturation, the cleaved N-terminal propeptide of VI is observed, reaching deep into the peripentonal hexon cavity, detached from the membrane-lytic domain, so that the latter can be released. Our results thus provide the molecular basis for the requirement of maturation cleavage of protein VI. This process is essential for untethering and release of the membrane-lytic region, which is known to mediate endosome rupture and delivery of partially disassembled virions into the host cell cytoplasm.

Original languageEnglish (US)
Pages (from-to)11715-11720
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number32
DOIs
StatePublished - Aug 12 2014
Externally publishedYes

Keywords

  • Cement protein scaffold
  • Human adenovirus
  • Structure-function relationships

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