Activation of a paramyxovirus fusion protein is modulated by inside-out signaling from the cytoplasmic tail

David Waning, Charles J. Russell, Theodore S. Jardetzky, Robert A. Lamb

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Many viruses have evolved fusion-mediating glycoproteins that couple the energy released from irreversible protein refolding to the work of membrane fusion. The viral fusion proteins require a triggering event to undergo a cascade of tightly regulated conformational changes. Different isolates of the paramyxovirus SV5 fusion (F) protein have either a short (20-residue) or long (42-residue) cytoplasmic tail (CT), and a long CT suppresses fusion activity in a sequence-specific manner. Addition of a domain to the F protein CT, which has the propensity to forma three-helix bundle, stabilizes the F protein and increases the energy required for fusion activation. Quantitative cell-cell fusion assays and measurement of ectodomain conformation by monoclonal antibody reactivity indicate that this suppression of fusion by the long CT or addition of a three-helix bundle occurs at a step preceding initial membrane merger. The data suggest that F protein activation involves CT signaling to the ectodomain.

Original languageEnglish (US)
Pages (from-to)9217-9222
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number25
DOIs
StatePublished - Jun 22 2004

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Viral Fusion Proteins
Proteins
Protein Refolding
Membrane Fusion
Cell Fusion
Glycoproteins
Monoclonal Antibodies
Viruses
Membranes

All Science Journal Classification (ASJC) codes

  • General

Cite this

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Activation of a paramyxovirus fusion protein is modulated by inside-out signaling from the cytoplasmic tail. / Waning, David; Russell, Charles J.; Jardetzky, Theodore S.; Lamb, Robert A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 25, 22.06.2004, p. 9217-9222.

Research output: Contribution to journalArticle

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