Homologs of the α- and β-subunits of mammalian brain platelet- activating factor acetylhydrolase Ib in the Drosophila melanogaster genome

Peter J. Sheffield, Sarah Garrard, Michal Caspi, Junken Aoki, Hiroyuki Arai, Urszula Derewenda, Keizo Inoue, Beat Suter, Orly Reiner, Zygmunt S. Derewenda

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

The mammalian intracellular brain platelet-activating factor acetylhydrolase, implicated in the development of cerebral cortex, is a member of the phospholipase A2 superfamily. It is made up of a homodimer of the 45 kDa LIS1 protein (a product of the causative gene for type I lissencephaly) and a pair of homologous 26-kDa α-subunits which account for all the catalytic activity. LIS1 is hypothesized to regulate nuclear movement in migrating neurons through interactions with the cytoskeleton, while the α-subunits, whose structure is known, contain a trypsin-like triad within the framework of a unique tertiary fold. The physiological significance of the association of the two types of subunits is not known. In an effort to better understand the function of the complex we turned to genomic data mining in search of related proteins in lower eukaryotes. We found that the Drosophila melanogaster genome contains homologs of both a- and β-subunits, and we cloned both genes. The α-subunit homolog has been overexpressed, purified and crystallized. It lacks two of the three active-site residues and, consequently, is catalytically inactive against PAF-AH (Ib) substrates. Our study shows that the β-subunit homolog is highly conserved from Drosophila to mammals and is able to interact with the mammalian α-subunits but is unable to interact with the Drosophila α-subunit. (C) 2000 Wiley- Liss, Inc.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalProteins: Structure, Function and Genetics
Volume39
Issue number1
DOIs
Publication statusPublished - 2000 Apr 1
Externally publishedYes

Keywords

  • LIS1
  • PAF-AH(Ib)
  • α-subunit

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

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