Mutagenesis of phospholipase D defines a superfamily including a trans-Golgi viral protein required for poxvirus pathogenicity

Tsung Chang Sung, Rachel L. Roper, Yue Zhang, Simon A. Rudge, Ryan Temel, Scott M. Hammond, Andrew J. Morris, Bernard Moss, JoAnne Engebrecht, Michael A. Frohman

Research output: Contribution to journalArticle

291 Scopus citations

Abstract

Phospholipase D (PLD) genes are members of a superfamily that is defined by several highly conserved motifs. PLD in mammals has been proposed to play a role in membrane vesicular trafficking and signal transduction. Using site-directed mutagenesis, 25 point mutants have been made in human PLD1 (hPLD1) and characterized. We find that a motif (HxKxxxxD) and a serine/threonine conserved in all members of the PLD superfamily are critical for PLD biochemical activity, suggesting a possible catalytic mechanism. Functional analysis of catalytically inactive point mutants for yeast PLD demonstrates that the meiotic phenotype ensuing from PLD deficiency in yeast derives from a loss of enzymatic activity. Finally, mutation of an HxKxxxxD motif found in a vaccinia viral protein expressed in the Golgi complex results in loss of efficient vaccinia virus cell-to-cell spreading, implicating the viral protein as a member of the superfamily and suggesting that it encodes a lipid modifying or binding activity. The results suggest that vaccinia virus and hPLD1 may act through analogous mechanisms to effect viral cellular egress and vesicular trafficking, respectively.

Original languageEnglish (US)
Pages (from-to)4519-4530
Number of pages12
JournalEMBO Journal
Volume16
Issue number15
DOIs
StatePublished - Aug 1 1997
Externally publishedYes

Keywords

  • Phospholipase D (PLD)
  • SPO14
  • Vaccinia virus
  • VP37

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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