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Publication Abstract from PubMed

Determining the structure of the ligand-binding domain of the nicotinic acetylcholine receptor (nAChR) has been a long standing goal in the design of selective drugs useful in implicated diseases for this prevalent receptor family. Acetylcholine-binding proteins have proven to be valuable surrogates with structural similarity and sequence identity to the extracellular domain of the nicotinic receptor, yet these soluble proteins have their unique features and do not serve as exact replicates of the nAChRs of interest. Here we systematically modify the sequence of these proteins toward the homomeric human alpha7 nAChR. These chimeric proteins exhibit a shift in affinities to reflect alpha7 binding characteristics yet maintain expression levels and stability conducive for crystallization. We also present a pentameric humanoid nAChR extracellular domain with the structural determination of the alpha7 nAChR glycosylation site.

Creating an alpha7 nicotinic acetylcholine recognition domain from the acetylcholine-binding protein: crystallographic and ligand selectivity analyses.,Nemecz A, Taylor P J Biol Chem. 2011 Dec 9;286(49):42555-65. Epub 2011 Oct 18. PMID:22009746^[1]

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