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Common EF‐hand motifs in cholinesterases and neuroligins suggest a role for Ca 2+ binding in cell surface associations
Author(s) -
Tsigelny I.,
Taylor P.,
Bourne P.E.,
Shindyalov I.N.,
Südhof T.C.
Publication year - 2000
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.9.1.180
Subject(s) - neuroligin , neurexin , torpedo , biology , hydrolase , binding site , structural similarity , acetylcholinesterase , protein family , stereochemistry , biochemistry , receptor , chemistry , enzyme , gene , acetylcholine receptor , excitatory postsynaptic potential , postsynaptic potential
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 Zn 2+ found in the heavy metal replacement structure. Further, the interaction of neuroligin 1 with its cognate receptor neurexin depends on Ca 2+ . Thus, members of the α, β hydrolase fold family of proteins contain potential Ca 2+ binding sites, which in some family members may be critical for heterologous cell associations.