4aod

Publication Abstract from PubMed

Nicotinic acetylcholine receptors (nAChR) play important neurophysiological roles and are of considerable medical relevance. They have been studied extensively, greatly facilitated by the gastropod acetylcholine-binding proteins (AChBP) which represent soluble structural and functional homologues of the ligand-binding domain of nAChR. All these proteins are ring-like pentamers. Here we report that AChBP exists in the hemolymph of the planorbid snail Biomphalaria glabrata (vector of the schistosomiasis parasite) as a regular pentagonal dodecahedron, 22 nm in diameter (12 pentamers, 60 active sites). We sequenced and recombinantly expressed two approximately 25 kDa polypeptides (BgAChBP1 and BgAChBP2) with a specific active site, N-glycan site and disulfide bridge variation. We also provide the exon/intron structures. Recombinant BgAChBP1 formed pentamers and dodecahedra, recombinant BgAChBP2 formed pentamers and probably disulfide-bridged di-pentamers, but not dodecahedra. Three-dimensional electron cryo-microscopy (3D-EM) yielded a 3D reconstruction of the dodecahedron with a resolution of 6 A. Homology models of the pentamers docked to the 6 A structure revealed opportunities for chemical bonding at the inter-pentamer interfaces. Definition of the ligand-binding pocket and the gating C-loop in the 6 A structure suggests that 3D-EM might lead to the identification of functional states in the BgAChBP dodecahedron.

Acetylcholine-Binding Protein in the Hemolymph of the Planorbid Snail Biomphalaria glabrata Is a Pentagonal Dodecahedron (60 Subunits).,Saur M, Moeller V, Kapetanopoulos K, Braukmann S, Gebauer W, Tenzer S, Markl J PLoS One. 2012;7(8):e43685. Epub 2012 Aug 20. PMID:22916297^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.