Characterization of the apoptosis suppressor protein p49 from the Spodoptera littoralis nucleopolyhedrovirus

Zifei Pei, Galit Reske, Qihong Huang, Bruce D. Hammock, Yipeng Qi, Nor Chejanovsky

Research output: Contribution to journalArticle

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Abstract

Two antiapoptotic types of genes, iap and p35, were found in baculoviruses. P35 is a 35.kDa protein that can suppress apoptosis induced by virus infection or by diverse stimuli in vertebrates or invertebrates. iap homologues were identified in insects and mammals. Recently, we have identified sl-p49, a novel apoptosis suppressor gene and the first homologue of p35, in the genome of the Spodoptera littoralis nucleopolyhedrovirus. Here we show that sl-p49 encodes a 49-kDa protein, confirmed its primary structure that displays 48.8% identity to P35, and performed computer-assisted modeling of P49 based on the structure of P35. We demonstrated that P49 is able to inhibit insect and human effector caspases, which requires P49 cleavage at Asp94. Finally we identified domains important for P49's anti-apoptotic function that include a reactive site loop (RSL) protruding from a β-barrel domain. RSL begins at an amphipathic α1 helix, traverses the β-sheet central region, exposing Asp94 at the apex, and rejoins the β-barrel. Our model predicted seven α-helical motifs, three of them unique to P49. α-Helical motifs a1, a2, and a4 were required for P49 function. The high structural homology between P49 and P35 suggests that these molecules bear a scaffold common to baculovirus "apoptotic suppressor" proteins. P49 may serve as a novel tool to analyze the contribution of different components of the caspase chain in the apoptotic response in organisms not related phylogenetically.

Original languageEnglish (US)
Pages (from-to)48677-48684
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number50
DOIs
StatePublished - Dec 13 2002

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Genes
Baculoviridae
Apoptosis
Insects
Catalytic Domain
Effector Caspases
Suppressor Genes
Nucleopolyhedrovirus
Spodoptera
Proteins
Mammals
Virus Diseases
Invertebrates
Caspases
Viruses
Scaffolds
Vertebrates
Genome
Molecules
Spodoptera littoralis nucleopolyhedrovirus P49 protein

ASJC Scopus subject areas

  • Biochemistry

Cite this

Characterization of the apoptosis suppressor protein p49 from the Spodoptera littoralis nucleopolyhedrovirus. / Pei, Zifei; Reske, Galit; Huang, Qihong; Hammock, Bruce D.; Qi, Yipeng; Chejanovsky, Nor.

In: Journal of Biological Chemistry, Vol. 277, No. 50, 13.12.2002, p. 48677-48684.

Research output: Contribution to journalArticle

Pei, Zifei ; Reske, Galit ; Huang, Qihong ; Hammock, Bruce D. ; Qi, Yipeng ; Chejanovsky, Nor. / Characterization of the apoptosis suppressor protein p49 from the Spodoptera littoralis nucleopolyhedrovirus. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 50. pp. 48677-48684.
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