Brain acetylhydrolase that inactivates platelet-activating factor is a G-protein-like trimer

Yew S. Ho, Lora Swenson, Urszula Derewenda, Laurence Serre, Yunyi Wei, Zbyszek Dauter, Mitsuharu Hattori, Tomoya Adachi, Junken Aoki, Hiroyuki Arai, Keizo Inoue, Zygmunt S. Derewenda

Research output: Contribution to journalArticlepeer-review

152 Citations (Scopus)

Abstract

THE platelet-activating factor PAF (1-O-alkyl-2-acetyl-sn-glycero3- phosphocholine) is a potent lipid first messenger active in general cell activation, fertilization, inflammatory and allergic reactions, asthma, HIV pathogenesis, carcinogenesis, and apoptosis. There is substantial evidence that PAF is involved in intracellular signalling, but the pathways are poorly understood. Inactivation of PAF is carried out by specific intra- and extracellular acetylhydrolases (PAF-AHs), a subfamily of phospholipases A2 that remove the sn-2 acetyl group. Mammalian brain contains at least three intracellular isoforms, of which PAF-AH(Ib) is the best characterized. This isoform contains a heterodimer of two homologous catalytic subunits α1 and α2, each of relative molecular mass 26K, and a non-catalytic 45K β- subunit, a homologue of the β-subunit of trimeric G proteins. We now report the crystal structure of the bovine α1 subunit of PAF-AH(Ib) at 1.7 Å resolution in complex with a reaction product, acetate. The tertiary fold of this protein is closely reminiscent of that found in p21(ras) and other GTPases. The active site is made up of a trypsin-like triad of Ser 47, His 195 and Asp 192. Thus, the intact PAF-AH(Ib) molecule is an unusual G- protein-like (α12)β trimer.

Original languageEnglish
Pages (from-to)89-93
Number of pages5
JournalNature
Volume385
Issue number6611
DOIs
Publication statusPublished - 1997 Jan 2
Externally publishedYes

ASJC Scopus subject areas

  • General

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