title: Common EF-hand motifs in cholinesterases and neuroligins suggest a role for Ca2+ binding in cell surface associations.
abstract: Comparisons of protein sequence via cyclic training of Hidden Markov Models (HMMs) in conjunction with alignments of three-dimensional structure, using the Combinatorial Extension (CE) algorithm, reveal two putative EF-hand metal binding domains in acetylcholinesterase. Based on sequence similarity, putative EF-hands are also predicted for the neuroligin family of cell surface proteins. These predictions are supported by experimental evidence. In the acetylcholinesterase crystal structure from Torpedo californica, the first putative EF-hand region binds the Zn2+ found in the heavy metal replacement structure. Further, the interaction of neuroligin 1 with its cognate receptor neurexin depends on Ca2+. Thus, members of the alpha,beta hydrolase fold family of proteins contain potential Ca2+ binding sites, which in some family members may be critical for heterologous cell associations.
authors.affiliation: Department of Pharmacology, University of California, San Diego, La Jolla 92093-0654, USA. itsigeln@ucsd.edu
authors.forename: I
authors.initials: I
authors.lastname: Tsigelny
authors.forename: I N
authors.initials: IN
authors.lastname: Shindyalov
authors.forename: P E
authors.initials: PE
authors.lastname: Bourne
authors.forename: T C
authors.initials: TC
authors.lastname: Südhof
authors.forename: P
authors.initials: P
authors.lastname: Taylor
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002135:Calcium-Binding Proteins / Q000737:chemistry*; D002802:Cholinesterases / Q000737:chemistry*; D020832:EF Hand Motifs; D008390:Markov Chains; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
chemical_list: D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D002802:Cholinesterases