title: Interactions underlying subunit association in cholinesterases.
abstract: Cholinesterases occur in a family of molecular forms, both as homo-oligomers of catalytic subunits, which can be either soluble, amphiphilic or lipid-anchored to the membrane; and hetero-oligomers of catalytic subunits and structural subunits. The structural subunits afford a method for precise localization of cholinesterases for specific function. A number of mutagenesis studies suggest that the C-terminal region of one alternatively spliced form of cholinesterase is involved in association of catalytic subunits into tetramers and in the association of these tetramers with structural subunits, however, there is currently no structural information about this region. In addition, none of the mutagenesis studies have clearly defined the residues important in these interactions. Here, multiple sequence alignment, structure prediction techniques and analysis of three-dimensional structural data are combined with a re-examination of mutagenesis and biochemical data. Three-dimensional models for the C-terminal region and for soluble tetrameric cholinesterase are proposed, and a set of rules governing subunit association are formulated. The simple model for association of catalytic and structural subunits presented is consistent with data for all known cholinesterases from species as divergent as nematode and man.
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: K
authors.initials: K
authors.lastname: Giles
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002802:Cholinesterases / Q000737:chemistry* / Q000235:genetics; D019281:Dimerization; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D014101:Torpedo
chemical_list: D002802:Cholinesterases