Author
Listed:
- 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
Institute de Biologie Structurale (IBS))
- 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)
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.
Suggested Citation
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, 1997.
"Brain acetylhydrolase that inactivates platelet-activating factor is a G-protein-like trimer,"
Nature, Nature, vol. 385(6611), pages 89-93, January.
Handle:
RePEc:nat:nature:v:385:y:1997:i:6611:d:10.1038_385089a0
DOI: 10.1038/385089a0
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