Selective removal of FG repeat domains from the nuclear pore complex by enterovirus 2Apro

Nogi Park, Nicholas J. Schweers, Kurt E Gustin

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Enteroviruses proteolyze nuclear pore complex (NPC) proteins (Nups) during infection, leading to disruption of host nuclear transport pathways and alterations in nuclear permeability. To better understand how enteroviruses exert these effects on nuclear transport, the mechanisms and consequences of Nup98 proteolysis were examined. The results indicate that Nup98 is rapidly targeted for degradation following enterovirus infection and that this is mediated by the enterovirus 2A protease (2Apro).Incubation of bacterially expressed or in vitro-translated Nup98 with 2Apro results in proteolytic cleavage at multiple sites in vitro, indicating that 2Apro cleaves Nup98 directly. Site-directed mutagenesis of putative cleavage sites identified Gly374 and Gly552 as the sites of 2Apro proteolysis in Nup98 in vitro and in infected cells. Indirect immunofluorescence assays using an antibody that recognizes the N terminus of Nup98 revealed that proteolysis releases the N-terminal FG-rich region from the NPC. In contrast, similar analyses using an antibody to the C terminus indicated that this region is retained at the nuclear rim. Nup88, a core NPC component that serves as a docking site for Nup98, also remains at the NPC in infected cells. These findings support a model whereby the selective removal of Nup FG repeat domains leads to increased NPCpermeability and inhibition of certain transport pathways, while retention of structural domains maintains the overall NPC structure and leaves other transport pathways unaffected.

Original languageEnglish (US)
Pages (from-to)11069-11079
Number of pages11
JournalJournal of Virology
Volume89
Issue number21
DOIs
StatePublished - 2015

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nucleoporins
Nuclear Pore
Enterovirus
Peptide Hydrolases
proteinases
Proteolysis
Cell Nucleus Active Transport
proteolysis
Nuclear Pore Complex Proteins
Enterovirus Infections
Antibodies
Indirect Fluorescent Antibody Technique
Site-Directed Mutagenesis
antibodies
site-directed mutagenesis
Permeability
infection
fluorescent antibody technique
permeability
cells

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Selective removal of FG repeat domains from the nuclear pore complex by enterovirus 2Apro . / Park, Nogi; Schweers, Nicholas J.; Gustin, Kurt E.

In: Journal of Virology, Vol. 89, No. 21, 2015, p. 11069-11079.

Research output: Contribution to journalArticle

Park, Nogi ; Schweers, Nicholas J. ; Gustin, Kurt E. / Selective removal of FG repeat domains from the nuclear pore complex by enterovirus 2Apro In: Journal of Virology. 2015 ; Vol. 89, No. 21. pp. 11069-11079.
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