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 and Zygmunt S. Derewenda
Additional contact information
Yew S. Ho: University of Virginia Health Sciences Center
Lora Swenson: University of Virginia Health Sciences Center
Urszula Derewenda: University of Virginia Health Sciences Center
Laurence Serre: University of Virginia Health Sciences Center
Yunyi Wei: University of Virginia Health Sciences Center
Zbyszek Dauter: University of Virginia Health Sciences Center
Mitsuharu Hattori: University of Virginia Health Sciences Center
Tomoya Adachi: University of Virginia Health Sciences Center
Junken Aoki: University of Virginia Health Sciences Center
Hiroyuki Arai: University of Virginia Health Sciences Center
Keizo Inoue: University of Virginia Health Sciences Center
Zygmunt S. Derewenda: University of Virginia Health Sciences Center

Nature, 1997, vol. 385, issue 6611, 89-93

Abstract: Abstract THE platelet-activating factor PAF (l-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a potent lipid first messenger active in general cell activation, fertilization, inflammatory and allergic reactions, asthma, HIV pathogenesis, carcinogenesis, and apoptosis1–5. 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 acetylhydrolases6 (PAF-AHs), a subfamily of phospho-lipases A2 that remove the sn-2 acetyl group. Mammalian brain contains at least three intracellular isoforms, of which PAF-AH(Ib) is the best characterized7–9. 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 p21ras 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 (α1/α2)β trimer.

Date: 1997
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DOI: 10.1038/385089a0

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